Anti-Aging
Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty
Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.
A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.
Stem Cells and Aging
The potential of stem cells to overcome age-related deteriorations of the body in regenerative medicine
Effects of nutritional components on aging
Nutrients including carbohydrates, proteins, lipids, vitamins, and minerals regulate various physiological processes and are essential for the survival of organisms. Reduced overall caloric intake delays aging in various organisms
Exercise Attenuates the Major Hallmarks of Aging
Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people.
Aging Hallmarks: The Benefits of Physical Exercise
World population has been continuously increasing and progressively aging. Aging is characterized by a complex and intraindividual process associated with nine major cellular and molecular hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, a loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This review exposes the positive antiaging impact of physical exercise at the cellular level, highlighting its specific role in attenuating the aging effects of each hallmark
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Aging tissues experience a progressive decline in homeostatic and regenerative capacities, which has been attributed to degenerative changes in tissue-specific stem cells, stem cell niches and systemic cues that regulate stem cell activity.
Spinal Muscular Atrophy
Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era
Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. In this review we provide an update regarding the most common form of SMA, proximal or 5q SMA, and discuss the contemporary approach to diagnosis and treatment
Advances in modeling and treating spinal muscular atrophy
Spinal muscular atrophy (SMA) is an inherited childhood neurodegenerative disorder caused by ubiquitous deficiency of the survival motor neuron (SMN) protein—the hallmarks of which are the selective loss of motor neurons and skeletal muscle atrophy.
Treatment of Spinal Muscolar Atrophy with Intrathecal Mesenchymal Cells
SMA1 is a genetic disease that leads to a progressive apoptosis of the second motoneuron and then to a complete paralysis. There are reports of efficacy of mesenchymal cells in the treatment of other neurological diseases; therefore we decided to treat some children with these cells.
Stem cell model of spinal muscular atrophy
Human embryonic stem cells provide a useful source of material for studying basic human development and various disease states. However, ethical issues concerning their procurement limit their acceptance and possible clinical applicability.
Autism
Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism
Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease
Autologous bone marrow mononuclear cell therapy for autism: an open label proof of concept study
Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain.
Human Embryonic Stem Cells in the Treatment of Autism: A Case Series
Autism spectrum disorder is a neurodevelopmental disorder accompanied by weak immune system and neuroinflammation. Multiple factors contribute to etiology of autism spectrum disorder including genetic disorders, environmental substances/toxins, imbalanced immune system, encephalitis, and viral infections. Autism spectrum disorder is an incurable disease;
Efficacy and Safety of Stem Cell Therapy in Children With Autism Spectrum Disorders: A Systematic Review and Meta-Analysis
There is insufficient evidence regarding the efficacy and safety of stem cell therapy for autism spectrum disorders. We performed the first meta-analysis of stem cell therapy for autism spectrum disorders in children to provide evidence for clinical rehabilitation.
Dietary interventions for autism spectrum disorder: An updated systematic review of human studies
Autism is a complex spectrum of disorders with genetic, epigenetic, autoimmune, oxidative stress, and environmental etiologies. Treatment of ASD using dietary approach is a promising strategy, especially owing to its safety and availability. Our study critically analysed the roles and efficacy of antioxidants, probiotics, prebiotics, camel milk and vitamin D.
Ataxia
Disorders of the Cerebellum: Ataxia, Dysmetria of Thought, and the Cerebellar Cognitive Affective Syndrome
Many diseases involve the cerebellum and produce ataxia, which is characterized by incoordination of balance, gait, extremity and eye movements, and dysarthria. Cerebellar lesions do not always manifest with ataxic motor syndromes, however. The cerebellar cognitive affective syndrome (CCAS) includes impairments in executive, visual-spatial, and linguistic abilities, with affective disturbance ranging from emotional blunting and depression, to disinhibition and psychotic features. The cognitive and psychiatric components of the CCAS, together with the ataxic motor disability of cerebellar disorders, are conceptualized within the dysmetria of thought hypothesis. This concept holds that a universal cerebellar transform facilitates automatic modulation of behavior around a homeostatic baseline, and the behavior being modulated is determined by the specificity of anatomic subcircuits, or loops, within the cerebrocerebellar system. Damage to the cerebellar component of the distributed neural circuit subserving sensorimotor, cognitive, and emotional processing disrupts the universal cerebellar transform, leading to the universal cerebellar impairment affecting the lesioned domain.
Falls in degenerative cerebellar ataxias
We retrospectively and prospectively assessed the frequency and characteristics of falls in patients with degenerative cerebellar ataxias. The results show that falls occur very frequently in patients with degenerative cerebellar ataxias and that these falls are serious and often lead to injuries or a fear of falling. Clinicians should be aware of this problem in ataxia patients and should try to prevent falls. © 2005 Movement Disorder Society
Ataxia
This article introduces the background and common etiologies of ataxia and provides a general approach to assessing and managing the patient with ataxia.
Spinocerebellar Ataxia
Ataxia is the absence of voluntary muscle coordination and loss of control of movement that affects gait stability, eye movement, and speech. Spinocerebellar ataxia (SCA) is an inherited (autosomal dominant), progressive, neurodegenerative, and heterogeneous disease that mainly affects the cerebellum.
Brain and induced pluripotent stem cell-derived neural stem cells
The ataxia telangiectasia mutated (ATM) kinase is a key transducer of the cellular response to DNA double strand breaks and its deficiency causes ataxia-telangiectasia (A-T), a pleiotropic genetic disorder primarily characterized by cerebellar neuropathy, immunodeficiency and cancer predisposition.
Clinical analysis of adult-onset spinocerebellar ataxias in Thailand
Non-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes.
Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial
The pleiotropic effects of riluzole may antagonize common mechanisms underlying chronic cerebellar ataxia, a debilitating and untreatable consequence of various diseases.
Diabetes
Pluripotent stem cell-derived pancreatic β-cells: potential for regenerative medicine in diabetes
Diabetes mellitus, which affects 346 million people, is one of the leading causes of death worldwide. Pancreatic β-cells, existing in the islets of Langerhans, play central roles in the progression of diabetes. An efficient strategy to produce functional pancreatic β-cells is important for both transplantation therapy and disease modeling of diabetes. Human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, provide unlimited starting materials to generate differentiated cells for regenerative studies. Significant progress has been made in human embryonic/induced pluripotent stem cell differentiation in the last several years.
Stem cells as a potential therapy for diabetes mellitus: a call-to-action in Latin America
Latin America is a fast-growing region that currently faces unique challenges in the treatment of all forms of diabetes mellitus. The burden of this disease will be even greater in the coming years due, in part, to the large proportion of young adults living in urban areas and engaging in unhealthy lifestyles. Unfortunately, the national health systems in Latin-American countries are unprepared and urgently need to reorganize their health care services to achieve diabetic therapeutic goals.
Mesenchymal Stem Cells as New Therapeutic Approach for Diabetes and Pancreatic Disorders
Diabetes is a worldwide disease which actually includes different disorders related to glucose metabolism. According to different epidemiological studies, patients affected by diabetes present a higher risk to develop both acute and chronic pancreatitis, clinical situations which, in turn, increase the risk to develop pancreatic cancer. Current therapies are able to adjust insulin levels according to blood glucose peak, but they only partly reach the goal to abrogate the consequent inflammatory milieu responsible for diabetes-related diseases.
Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data
Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs).
Therapeutic Potential of Mesenchymal Stem Cells for Diabetes
Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the capacity to secrete multiple biologic factors that can restore and repair injured tissues. Preclinical and clinical evidence have substantiated the therapeutic benefit of MSCs in various medical conditions. Currently, MSCs are the most commonly used cell-based therapy in clinical trials because of their regenerative effects, ease of isolation, and low immunogenicity. Experimental and clinical studies have provided promising results using MSCs to treat diabetes. This review will summarize the role of MSCs on tissue repair, provide emerging strategies to improve MSC function, and describe how these processes translate to clinical treatments for diabetes.
Therapeutic Potential of Wharton’s Jelly Mesenchymal Stem Cells for Diabetes: Achievements and Challenges
Diabetes mellitus (DM) is an alarming metabolic disease in which insulin secreting β-cells are damaged to various extent. Unfortunately, although currently available treatments help to manage the disease, however, patients usually develop complications, as well as decreased life quality and increased mortality. Thus, efficient therapeutic interventions to treat diabetes are urgently warranted. During the past years, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in various regenerative medicine applications. The main fascination about MSCs lies in their potential to exert reparative effects on an amazingly wide spectrum of tissue injury.
Stem cell therapy for diabetes
Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process.
Type 1 Diabetes
Stem cell treatment for type 1 diabetes
Type 1 diabetes mellitus (T1DM) is a common chronic disease in children, characterized by a loss of β cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy, and retinopathy.
Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetesLes cellules souches mésenchymateuses comme nouvelle approche thérapeutique du diabète de type 1
Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood
Current Status of Stem Cell Treatment for Type I Diabetes Mellitus
Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans.
Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus
Type 1 diabetes mellitus (T1DM) is caused by the autoimmune targeting of pancreatic β-cells, and, in the advanced stage, severe hypoinsulinemia due to islet destruction. In patients with T1DM, continuous exogenous insulin therapy cannot be avoided..
Type 2 Diabetes
Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes
Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) and impaired insulin secretion. The chronic inflammatory process contributed to IR and could also hamper pancreatic β cell function. However, currently applied treatment cannot reverse β cell damage or alleviate inflammation.
Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial
Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans.
Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study
There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease. This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation (ABMSCT) in T2DM.
Optic Atrophy
Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow derived stem cells in the treatment of Dominant Optic Atrophy
We report the results of 6 patients with Dominant Optic Atrophy (DOA) who met inclusion criteria and were treated in the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS/SCOTS 2 is an Institutional Review Board approved and NIH registered (NCT 03011541) clinical study that uses autologous bone marrow derived stem cells (BMSC) in the treatment of optic nerve and retinal disease.
Visual function in patients with optic nerve pallor (optic atrophy).
This cross-sectional study assessed the relationship between the degree of optic nerve pallor (optic atrophy) and visual function. Using a set of “gold standard” stereoscopic slides, the severity of optic atrophy for 270 eyes, each having sustained a bout of optic neuropathy, was graded.
Stem cells to replace the optic nerve
Methods that exist now and that might be developed are suggested to replace retinal ganglion cells and their axons in the optic nerve, ultimately to re-establish functional vision in eyes blind from glaucoma.
Stem cell treatment of degenerative eye disease
Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections.
Cell Replacement Therapy for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges
The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice.
Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report
In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867.
Optic Nerve Hypoplasia
Failure of stem cell therapy to improve visual acuity in children with optic nerve hypoplasia
To evaluate the effectiveness of stem cell therapy in improving visual acuity or optic nerve function in children with optic nerve hypoplasia (ONH).
Glaucoma Disease
Research progress of stem cells on glaucomatous optic nerve injury
Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury.
A Novel Glaucoma Approach: Stem Cell Regeneration of the Trabecular Meshwork
Glaucoma is the leading cause of global irreversible blindness, necessitating research for new, more efficacious treatment options than currently exist. Trabecular meshwork (TM) cells play an important role in the maintenance and function of the aqueous outflow pathway, and studies have found that there is decreased cellularity of the TM in glaucoma.
Stem cell therapy for glaucoma: possibilities and practicalities
Glaucoma is a progressive, neurodegenerative, optic neuropathy in which currently available therapies cannot always prevent, and do not reverse, vision loss. Stem cell transplantation may provide a promising new avenue for treating many presently incurable degenerative conditions, including glaucoma.
Stem cells for neuroprotection in glaucoma
Stem cell transplantation is currently being explored as a therapy for many neurodegenerative diseases including glaucoma. Cellular therapies have the potential to provide chronic neuroprotection after a single treatment, and early results have been encouraging in models of spinal cord injury and Parkinson’s disease.
The potential of stem cell research for the treatment of neuronal damage in glaucoma
Stem cell research offers a wide variety of approaches for the advancement of our understanding of basic mechanisms of neurodegeneration and tissue regeneration and for the discovery and development of new therapeutic strategies to prevent and restore neuronal cell loss.
Eye Disease
Stem cell treatment of degenerative eye disease
Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections.
Stem cells in the eye
In the adult organism, all tissue renewal and regeneration depends ultimately on somatic stem cells, and the eye is no exception. The importance of limbal stem cells in the maintenance of the corneal epithelium has long been recognised, and such cells are now used clinically for repair of a severely damaged cornea.
Stem Cells and Eye Development
Stem cells hold promise in the treatment of many different types of disease. The generation of induced pluripotent stem cells (iPSCs) by reprogramming somatic cells has provided unprecedented opportunities for studying basic biology and modeling human diseases. In addition, the differentiation of embryonic stem cells or iPSCs into different functional cell types also permits insights into disease mechanism.
Osteoarthritis
Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans
Adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy. With the recent demonstration of MSC homing properties, intravenous applications of MSCs to cell-damaged diseases have increased. In the present study, the toxicity and tumorigenicity of human AdMSCs (hAdMSCs) were investigated for clinical application.
Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study
Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging results in both animal studies and a few human case reports. We designed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells (MSCs) in humans and to obtain early efficacy information for this treatment.
Mesenchymal stem cells in osteoarthritis
Accumulating evidence indicates that every tissue contains stem cells. Our understanding of the biology of stem cells reveals that these cell populations have a critical role in the homeostasis and repair of tissues. Besides the local stem cell niches, additional compartments in the body such as the bone marrow may serve as reservoirs for stem cell populations. On more extensive tissue damage, and guided by local repair responses, “reparative” cell populations are mobilized from more distant stem cell reservoirs and migrate to the site of injury, thereby contributing in many aspects of local tissue repair.
Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis
In the present study, the clinical outcomes and second-look arthroscopic findings of intra-articular injection of stem cells with arthroscopic lavage for treatment of elderly patients with knee osteoarthritis (OA) were evaluated.
Mesenchymal stem cell therapy for osteoarthritis: current perspectives
Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease.
Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis
The aim of this study was to evaluate the therapeutic efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee osteoarthritis (OA).
Degenerative Disc Disease
Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for Degenerative Disc Disease
The intervertebral disc (IVD) is immensely important for the integrity of vertebral column function. The highly specialized IVD functions to confer flexibility and tensile strength to the spine and endures various types of biomechanical force.
Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells
Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs.
Stem cell therapy for degenerative disc disease
Low back pain is widely recognized as one of the most prevalent pathologies in the developed world. In the United States, low back pain is the most common health problem for adults under the age of 50, resulting in significant societal and personal costs.
Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy
Degenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management,
Orthopaedic Disease
Application of Stem Cells in Orthopedics
Stem cell research plays an important role in orthopedic regenerative medicine today. Current literature provides us with promising results from animal research in the fields of bone, tendon, and cartilage repair. While early clinical results are already published for bone and cartilage repair, the data about tendon repair is limited to animal studies.
Stem Cell Therapies in Orthopaedic Trauma
Stem cells offer great promise to help understand the normal mechanisms of tissue renewal, regeneration, and repair, and also for development of cell-based therapies to treat patients after tissue injury. Most adult tissues contain stem cells and progenitor cells that contribute to homeostasis, remodeling and repair.
The Current Role of Stem Cells in Orthopaedic Surgery
Basic science and experimental research on stem cells has increased exponentially in the last decade. Our present knowledge about stem cell biology is better than ever before. This new paradigm shift in research has been reflected in the field of orthopaedic surgery.
Stem cells in orthopaedics and fracture healing
Stem cell application is a burgeoning field of medicine that is likely to influence the future of orthopaedic surgery. Stem cells are associated with great promise and great controversy. For the orthopaedic surgeon, stem cells may change the way that orthopaedic surgery is practiced and the overall approach of the treatment of musculoskeletal disease.
Joint Disease
Mesenchymal stem cells in joint disease and repair
Osteoarthritis (OA), a prevalent chronic condition with a striking impact on quality of life, represents an enormous societal burden that increases greatly as populations age. Yet no approved pharmacological intervention, biologic therapy or procedure prevents the progressive destruction of the OA joint. Mesenchymal stem cells (MSCs)-multipotent precursors of connective tissue cells that can be isolated from many adult tissues, including those of the diarthrodial joint-have emerged as a potential therapy.
Knee Osteoarthritis
Stem cell application for osteoarthritis in the knee joint: A minireview
Knee osteoarthritis is a chronic, indolent disease that will affect an ever increasing number of patients, especially the elderly and the obese. It is characterized by degeneration of the cartilage substance inside the knee which leads to pain,
Combination of intra-articular autologous activated peripheral blood stem cells with growth factor addition
Trauma or osteoarthritis (OA) create articular cartilage defects that cannot efficiently heal, thus leading to significant long-term disability. Failed conservative treatment in cartilage diseases is a known condition that necessitates repair attempts but current methods are inadequate. Recent studies in OA animal models and humans, showed articular cartilage regeneration following combinations of drilling, adult stem cells, and intra-articular hyaluronic acid.
Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients
Osteoarthritis is a degenerative joint disease characterized by the destruction of joint cartilage. Mesenchymal stem cells (MSCs) are found in low numbers in normal cartilage, mainly in the superficial layer, acting as repairing agents.
Mesenchymal stem cells in knee osteoarthritis treatment: A systematic review and meta-analysis
Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a relatively new treatment and has not yet gained popularity. So, the effectiveness, safety and potential of mesenchymal stem cells (MSCs) for knee OA treatment is worthy to be explored.
Shoulder Injury
Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears
Recent studies report a relatively high failure rate for tendon-bone healing after rotator cuff repair. Several studies have investigated biologically augmented rotator cuff repair; however, none has shown the application of synovial mesenchymal stem cells for such repair.
Allogenous tendon stem/progenitor cells in silk scaffold for functional shoulder repair
Tendon stem/progenitor cells (TSPCs) were recently identified within tendon tissues. The aim of this study was to investigate TSPC-seeded knitted silk-collagen sponge scaffold for functional shoulder repair.
The future role of mesenchymal stem cells in the management of shoulder disorders
Biologics may help to optimize the healing environment after rotator cuff repair. Mesenchymal stem cells (MSCs) may have the potential to regenerate a physiological enthesis, thereby improving healing at the repair site after rotator cuff repair.
Osteoporosis
Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment
Osteoporosis is a progressive skeletal disease characterized by decreased bone mass and degraded bone microstructure, which leads to increased bone fragility and risks of bone fracture. Osteoporosis is generally age related and has become a major disease of the world.
Mesenchymal Stem Cells-Derived Exosomes: A Possible Therapeutic Strategy for Osteoporosis
Osteoporosis is a common age-related disorder characterized by low bone mass and deterioration in bone microarchitecture, leading to increased skeletal fragility and fracture risk. The pathophysiology of osteoporosis is multifactorial.
The future role of mesenchymal stem cells in the management of shoulder disorders
Biologics may help to optimize the healing environment after rotator cuff repair. Mesenchymal stem cells (MSCs) may have the potential to regenerate a physiological enthesis, thereby improving healing at the repair site after rotator cuff repair.
Osteoporosis treatment by mesenchymal stromal/stem cells and their exosomes: Emphasis on signaling pathways and mechanisms
Osteoporosis is the loss of bone density, which is one of the main problems in developed and developing countries and is more common in the elderly. Because this disease is often not diagnosed until a bone fracture, it can become a life-threatening disease and cause hospitalization.
Sports Injury
Mesenchymal Stem Cell Therapy in the Sports Knee
The relationship between biological tissue healing following knee injury or surgery and long-term clinical outcome has come to the forefront of sports medicine practice. This has led many knee surgeons to incorporate biologically mediated healing factors into the management of knee injuries. In particular, the clinical use of mesenchymal stem cells has opened new horizons.
Stem Cells for the Treatment of Skeletal Muscle Injury
Skeletal muscle injuries are extremely common, accounting for up to 35-55% of all sports injuries and quite possibly impacting all musculoskeletal traumas. These injuries result in the formation of fibrosis that may lead to development of painful contractures, increases their risk for repeat injuries, and limits their ability to return to a baseline or pre-injury level of function.
Prospect of mesenchymal stem cells in therapy of osteoporosis: A review
Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality.
Mesenchymal stem cell therapy for sports injuries
The number of sports-related injuries is on the rise as more people are involved in sports, especially the extreme sports that are prone to injury. A serious sports injury might end the career of an athlete. Thus, prompt and effective treatment is very important for these injuries.
Psoriasis
Mesenchymal stem cells and psoriasis: State of the art and future perspectives
Mesenchymal stem cells and psoriasis: State of the art and future perspectives
Mesenchymal stem cells for the treatment of psoriasis: a comprehensive review
Mesenchymal stem cells (MSCs) have recently been shown to have not only regenerative capabilities but also immunomodulating properties. For this reason, they are currently under investigation in clinical trials for the treatment of several autoimmune systemic disorders.
Stem cells in psoriasis
Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system.
Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy
Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-900 Olsztyn, Poland
Retinitis Pigmentosa
Bone marrow–derived stem cells preserve cone vision in retinitis pigmentosa
Retinitis pigmentosa is a heritable group of blinding diseases resulting from loss of photoreceptors, primarily rods and secondarily cones, that mediate central vision. Loss of retinal vasculature is a presumed metabolic consequence of photoreceptor degeneration. A new study shows that autologous bone marrow–derived lineage-negative hematopoietic stem cells, which incorporate into the degenerating blood vessels in two murine models of retinitis pigmentosa, rd1 and rd10, prevent cone loss. The use of autologous bone marrow might avoid problems with rejection while preserving central cone vision in a wide variety of genetically disparate retinal degenerative diseases.
Stem cell treatment of degenerative eye disease
Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC).
Recent advances of stem cell therapy for retinitis pigmentosa
Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials.
Bone Marrow-derived Mesenchymal Stem Cell Therapy in Retinitis Pigmentosa
To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa.
Stem cell therapy: a novel approach for vision restoration in retinitis pigmentosa
Unfortunately, at present, degenerative retinal diseases such as retinitis pigmentosa remains untreatable. Patients with these conditions suffer progressive visual decline resulting from continuing loss of photoreceptor cells and outer nuclear layers. However,
Stem cell transplantation as a progressing treatment for retinitis pigmentosa
Retinal degenerative diseases such as retinitis pigmentosa (RP) are of the major causes of vision loss in developed countries. Despite the unclear pathophysiology, treatment methods have been investigated vastly in the past decades.
Spinal Cord Injury
Phase I‐II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury
Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells).
A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury
The purpose of this study is to compare the therapeutic effects between autologous and allogenic bone-marrow-derived mesenchymal stem cell (MSC) transplantation in experimentally-induced spinal cord injury (SCI) of dogs. Thirty adult Beagle dogs (control group=10, autologous group=10, and allogenic group=10) were used in this study. Prelabeled MSCs were intrathecally transplanted through the lumbar spinal cord into the injured lesion at a density of 1 x 10(7) cells 7 days after SCI.
Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells
The purpose of this study was to observe the clinical effect and safety of umbilical cord mesenchymal stem cells (UC-MSCs) in treating spinal cord injury (SCI) by intrathecal injection.
Mesenchymal stem cell for prevention and management of intervertebral disc degeneration
Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.
Treatment of spinal cord injury with mesenchymal stem cells
Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life.
Stem Cell Therapy for Spinal Cord Injury
Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits.
Stem Cell–Based Therapies for Spinal Cord Injury
Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. There is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Transplantation of stem cells or progenitors may support spinal cord repair. Stem cells are characterized by self-renewal and their ability to become any cell in an organism. Promising results have been obtained in experimental models of SCI. Stem cells can be directed to differentiate into neurons or glia in vitro, which can be used for replacement of neural cells lost after SCI. Neuroprotective and axon regeneration-promoting effects have also been credited to transplanted stem cells.
Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials
Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine.
Progress in Stem Cell Therapy for Spinal Cord Injury
Background. Spinal cord injury (SCI) is one of the serious neurological diseases that occur in young people with high morbidity and disability. However, there is still a lack of effective treatments for it. Stem cell (SC) treatment of SCI has gradually become a new research hotspot over the past decades. This article is aimed at reviewing the research progress of SC therapy for SCI. Methods. Review the literature and summarize the effects, strategies, related mechanisms, safety, and clinical application of different SC types and new approaches in combination with SC in SCI treatment. Results.
Advances in repair of spinal cord injury by transplantation of marrow mesenchymal stem cells
To review the advances in repair of spinal cord injury by transplantation of marrow mesenchymal stem cells (MSCs).
Stem cell transplantation for treating spinal cord injury
To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science.
ALS
ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells
Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy
Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine.
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
NurOwn, phase 2, randomized, clinical trial in patients with ALS
To determine the safety and efficacy of mesenchymal stem cell (MSC)-neurotrophic factor (NTF) cells (NurOwn®, autologous bone marrow-derived MSCs, induced to secrete NTFs) delivered by combined intrathecal and intramuscular administration to participants with amyotrophic lateral sclerosis (ALS) in a phase 2 randomized controlled trial.
Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS)
Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) – induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells
Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis
Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled. After a 3-month lead-in period, autologous MSCs were isolated two times from the BM at an interval of 26 days and were then expanded in vitro for 28 days and suspended in autologous cerebrospinal fluid. Of the 8 patients, 7 received 2 intrathecal injections of autologous MSCs (1 × 106 cells per kg) 26 days apart.
Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems.
Neuroprotective Potential of Cell-Based Therapies in ALS: From Bench to Bedside
Motor neurons (MN) degeneration is a main feature of amyotrophic lateral sclerosis (ALS), a neurological disorder with a progressive course. The diagnosis of ALS is essentially a clinical one. Most common symptoms include a gradual neurological deterioration that reflect the impairment and subsequent loss of muscle functions. Up-to-date ALS has no therapy that would prevent or cure a disease. Modern therapeutic strategies comprise of neuroprotective treatment focused on antiglutamatergic, antioxidant, antiapoptotic, and anti-inflammatory molecules.
Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans
Introduction: Recently it has been shown in animal models of amyotrophic lateral sclerosis (ALS) that stem cells significantly slow the progression of the disease and prolong survival. We have evaluated the feasibility and safety of a method of intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a few well-monitored patients with ALS.
Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS), formerly known as Lou Gehrig’s disease, is a neurological disorder that affects motor neurons, the nerve cells in the brain and spinal cord that control voluntary muscle movement and breathing.
The multifaceted role of kinases in amyotrophic lateral sclerosis: genetic, pathological and therapeutic implications
By reviewing recent findings on kinase function in ALS, Guo et al. show that kinases are implicated in ALS disease progression on three levels: a) genes encoding kinases are causal or risk genes in ALS; b) kinases interact with proteins encoded by ALS genes; and c) kinases participate in major ALS disease mechanisms.
The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis
Unfortunately and despite all efforts, amyotrophic lateral sclerosis (ALS) remains an incurable neurodegenerative disorder characterized by the progressive and selective death of motor neurons.
SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease presenting as sporadic (sALS) or familial (fALS) forms. Even if the list of the genes underlining ALS greatly expanded, defects in superoxide dismutase 1 (SOD1), encoding the copper/zinc SOD1
Calcium Dyshomeostasis and Lysosomal Ca2+ Dysfunction in Amyotrophic Lateral Sclerosis
Recent findings in the understanding of amyotrophic lateral sclerosis (ALS) revealed that alteration in calcium (Ca2+) homeostasis may largely contribute to motor neuron demise. A large part of these alterations is due to dysfunctional Ca2+-storing organelles, including the endoplasmic reticulum (ER) and mitochondria.
Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans
Introduction: Recently it has been shown in animal models of amyotrophic lateral sclerosis (ALS) that stem cells significantly slow the progression of the disease and prolong survival. We have evaluated the feasibility and safety of a method of intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a few well-monitored patients with ALS.
Alzheimer’s
Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview
Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells
Immunomodulatory role of mesenchymal stem cells in Alzheimer's disease
Alzheimer’s disease (AD) is one of the most common causes of dementia and is characterized by gradual loss in memory, language, and cognitive function. The hallmarks of AD include extracellular amyloid deposition, intracellular neuronal fiber entanglement, and neuronal loss. Despite strenuous efforts toward improvement of AD,
Stem cell therapies for Alzheimer's disease is it time?
Stem cell therapy has the potential to modify the disease of Alzheimer’s disease. This article aims to describe the mechanisms of action, preclinical animal studies, human clinical trials, and challenges for the future direction of stem cell therapy for Alzheimer’s disease.
Stem cell therapy in Alzheimer's disease: possible benefits and limiting drawbacks
Alzheimer’s disease (AD) is the sixth leading cause of death globally and the main reason for dementia in elderly people. AD is a long-term and progressive neurodegenerative disorder that steadily worsens memory and communicating skills eventually leads to a disabled person of performing simple daily tasks. Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating the regeneration of already-damaged neural cells, and merely provide symptomatic relief. Therefore, a deeper understanding of the mechanism of action of stem cell may contribute to the development of novel and effective therapies.
Alzheimer's Disease and Stem Cell Therapy
The loss of neuronal cells in the central nervous system may occur in many neurodegenerative diseases. Alzheimer’s disease is a common senile disease in people over 65 years, and it causes impairment characterized by the decline of mental function, including memory loss and cognitive impairment, and affects the quality of life of patients. However, the current therapeutic strategies against AD are only to relieve symptoms, but not to cure it. Because there are only a few therapeutic strategies against Alzheimer’s disease, we need to understand the pathogenesis of this disease. Cell therapy may be a powerful tool for the treatment of Alzheimer’s disease. This review will discuss the characteristics of Alzheimer’s disease and various available therapeutic strategies.
Stem cell therapy for Alzheimer's disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. It is caused by synaptic failure and excessive accumulation of misfolded proteins. To date, almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD. Also, currently available drug candidates intervene too late. Stem cells have improved characteristics of self-renewal, proliferation, differentiation, and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells. Stem cell treatment has been successful in AD animal models. Recent preclinical studies on stem cell therapy for AD have proved to be promising.
Stem Cell Treatment for Alzheimer’s Disease
Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
COPD
Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.
Stem cell therapies for chronic obstructive pulmonary disease: current status of pre-clinical studies and clinical trials
Chronic obstructive pulmonary disease (COPD) is a respiratory disease that has a major impact worldwide. The currently-available drugs mainly focus on relieving the symptoms of COPD patients. Novel regenerative therapeutic approaches have been investigated with the aim of repairing or replacing the injured functional structures of the respiratory system. We summarized the progress made by regenerative therapies for COPD by analyzing results from both pre-clinical studies and completed clinical trials. These approaches include the application of exogenous stem cells or small molecules to stimulate the regeneration by endogenous lung stem/progenitor cells.
Mesenchymal stem cells and immunomodulation: current status and future prospects
The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.
Can Youthful Mesenchymal Stem Cells from Wharton’s Jelly Bring a Breath of Fresh Air for COPD?
Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality, projected to become the 3rd cause of disease mortality worldwide by 2020. COPD is characterized by persistent and not fully reversible airflow limitation that is usually progressive and is associated with an abnormal chronic inflammatory response of the lung to noxious agents including cigarette smoke. Currently available therapeutic strategies aim to ease COPD symptoms but cannot prevent its progress or regenerate physiological lung structure or function.
Mesenchymal Stem Cell Administration in Patients with Chronic Obstructive Pulmonary Disease
Patients with chronic obstructive pulmonary disease (COPD) have chronic, irreversible airway inflammation; currently, there is no effective or curative treatment and the main goals of COPD management are to mitigate symptoms and improve patients’ quality of life. Stem cell based therapy offers a promising therapeutic approach that has shown potential in diverse degenerative lung diseases. Preclinical studies have demonstrated encouraging outcomes of mesenchymal stem/stromal cells (MSCs) therapy for lung disorders including emphysema
Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell
Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung.
Mesenchymal stromal cell therapy in COPD: from bench to bedside
COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality. The major risk factor for COPD development is cigarette smoke, and the most efficient treatment for COPD is smoking cessation. However, even after smoking cessation, inflammation, apoptosis, and oxidative stress may persist and continue contributing to disease progression. Although current therapies for COPD (primarily based on anti-inflammatory agents) contribute to the reduction of airway obstruction and minimize COPD exacerbations, none can avoid disease progression or reduce mortality. Within this context, recent advances in mesenchymal stromal cell (MSC) therapy have made this approach a strong candidate for clinical use in the treatment of several pulmonary diseases.
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD)
Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin
Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis
In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.
Asthma
Small extracellular vesicles derived from human MSCs prevent allergic airway inflammation via immunomodulation on pulmonary macrophages
Allergic airway inflammation is a major public health disease that affects up to 300 million people in the world. However, its management remains largely unsatisfactory. The dysfunction of pulmonary macrophages contributes greatly to the development of allergic airway inflammation. It has been reported that small extracellular vesicles derived from mesenchymal stromal cells (MSC-sEV) were able to display extensive therapeutic effects in some immune diseases.
Mesenchymal Stem Cells Recruit CCR2+ Monocytes to Suppress Allergic Airway Inflammation
Mesenchymal stem cells (MSC) exert immune modulatory properties and previous studies demonstrated suppressive effects of MSC treatment in animal models of allergic airway inflammation. However, the underlying mechanisms have not been fully elucidated. We studied the role of MSC in immune activation and subsequent recruitment of monocytes in suppressing airway hyperresponsiveness and airway inflammation using a mouse model of allergic airway inflammation. MSC administration prior to or after allergen challenge inhibited the development of airway inflammation in allergen-sensitized mice.
The development of allergic inflammation
Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation.
Small extracellular vesicles derived from human MSCs prevent allergic airway inflammation via immunomodulation on pulmonary macrophages
Allergic airway inflammation is a major public health disease that affects up to 300 million people in the world. However, its management remains largely unsatisfactory. The dysfunction of pulmonary macrophages contributes greatly to the development of allergic airway inflammation.
Mesenchymal Stem Cells Suppress Severe Asthma by Directly Regulating Th2 Cells and Type 2 Innate Lymphoid Cells
Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma
Autoimmune
Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD).
Evaluation of the Therapeutic Potential of Mesenchymal Stem Cells (MSCs) in Preclinical Models of Autoimmune Diseases
Autoimmune diseases, chronic in nature, are generally hard to alleviate. Present long-term treatments with available drugs such as steroids, immune-suppressive drugs, or antibodies have several debilitating side effects.
RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner.
Cardiovascular Disease
Cardiac stem cells and their roles in myocardial infarction
Myocardial infarction leads to loss of cardiomyocytes, scar formation, ventricular remodeling and eventually deterioration of heart function. Over the past decade, stem cell therapy has emerged as a novel strategy for patients with ischemic heart disease and its beneficial effects have been demonstrated by substantial preclinical and clinical studies.
Myocardial infarction: stem cell transplantation for cardiac regeneration
Autoimmune diseases, chronic in nature, are generally hard to alleviate. Present long-term treatments with available drugs such as steroids, immune-suppressive drugs, or antibodies have several debilitating side effects.
COVID-19
Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series
Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients.
Promising role for mesenchymal stromal cells in coronavirus infectious disease-19 (COVID-19)-related severe acute respiratory syndrome?
Mesenchymal stromal cells (MSC) have immune regulatory and tissue regenerative properties. MSCs are being studied as a therapy option for many inflammatory and immune disorders and are approved to treat acute graft-versus-host disease (GvHD). The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic and associated coronavirus infectious disease-19 (COVID-19) has claimed many lives. Innovative therapies are needed. Preliminary data using MSCs in the setting of acute respiratory distress syndrome (ARDS) in COVID-19 are emerging. We review mechanisms of action of MSCs in inflammatory and immune conditions and discuss a potential role in persons with COVID-19.
Taming of Covid-19: potential and emerging application of mesenchymal stem cells
Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has turned out to cause a pandemic, with a sky scraping mortality. The virus is thought to cause tissue injury by affecting the renin-angiotensin system. Also, the role of the over-activated immune system is noteworthy, leading to severe tissue injury via the cytokine storms.
Therapeutic implications of mesenchymal stem cells in acute lung injury/acute respiratory distress syndrome
Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. Current treatment of ALI/ARDS is primarily supportive, with lung protective ventilation and fluid conserving strategies. Despite improvement in these strategies, recent data indicate that the mortality of ALI/ARDS is still as high as 30 to 50%.
Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients
In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate.
Stem cell therapy for COVID-19 and other respiratory diseases: Global trends of clinical trials
Respiratory diseases, including coronavirus disease 2019 and chronic obstructive pulmonary disease (COPD), are leading causes of global fatality. There are no effective and curative treatments, but supportive care only. Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses, as proved by accumulating preclinical studies. Stem cells consist of totipotent, pluripotent, multipotent, and unipotent cells with the potential to differentiate into cell types requested for repair. Mesenchymal stromal cells, endothelial progenitor cells, peripheral blood stem cells, and lung progenitor cells have been applied to clinical trials. To date
Crohn’s Disease
Immune modulation by mesenchymal stem cells
Mesenchymal stem cells (MSCs) can be derived from various adult tissues with multipotent and self‐renewal abilities. The characteristics of presenting no major ethical concerns, having low immunogenicity and possessing immune modulation functions make MSCs promising candidates for stem cell therapies. MSCs could promote inflammation when the immune system is underactivated and restrain inflammation when the immune system is overactivated to avoid self‐overattack. These cells express many immune suppressors to switch them from a pro‐inflammatory phenotype to an anti‐inflammatory phenotype, resulting in immune effector cell suppression and immune suppressor cell activation. We would discuss the mechanisms governing the immune modulation function of these cells in this review, especially the immune‐suppressive effects of MSCs.
Shattering barriers toward clinically meaningful MSC therapies
More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.
Mesenchymal Stem Cells for Perianal Crohn’s Disease
Perianal fistulizing Crohn’s disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.
Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial
Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD.
Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows
Mesenchymal stromal cells: clinical challenges and therapeutic opportunities
Mesenchymal Stromal Cells (MSCs) have been the subject of clinical trials for more than a generation and the outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. In this perspective, important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analysis of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.
Efficacy of stem cells therapy for Crohn’s fistula: a meta-analysis and systematic review
Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn’s fistula.
Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn’s disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact
Crohn’s disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application.
Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial
Complex perianal fistulas in Crohn’s disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn’s disease.
Fibromyalgia
Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic disease without definite etiology characterized by bladder-related pelvic pain. IC/BPS is associated with pain that negatively affects the quality of life. There are various therapeutic approaches against IC/BPS. However, no efficient therapeutic agent against IC/BPS has been discovered yet.
The association between pain and sleep in fibromyalgia
Electronic databases, including PsycINFO, the Cochrane database for systematic reviews, PubMed, EMBASE, and Ovid were searched to identify eligible articles. Databases independently screened and the quality of evidence using a reliable and valid quality assessment tool was assessed.
Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology
Fibromyalgia syndrome (FMS) is a chronic condition with unknown aetiology. The pathophysiology of the disease is incompletely understood; despite advances in our knowledge with regards to abnormal central and peripheral pain processing
Facts and myths pertaining to fibromyalgia
Heart Failure
Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue
Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles.
Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos) cells with markers of cardiac, vascular muscle, and endothelial lineages.
Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue
Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis
Mesenchymal Stem Cells in Cardiology
Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy.
Transplantation of mesenchymal stem cells for prevention of acute myocardial infarction induced heart failure: study protocol of a phase III randomized clinical trial (Prevent-TAHA8)
Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy.
Heart Disease
Stem Cell Treatment of the Heart
Stem cells are multipotent, undifferentiated cells capable of multiplication and differentiation. Preliminary experimental evidence suggests that stem cells derived from embryonic or adult tissues (especially bone marrow) may develop into myocardial cells.
Intramyocardial angiogenic cell precursor injection for cardiomyopathy
Stem cell therapy for heart failure is a rapidly progressing field. The objective of this study was to assess the safety, and short-term results of thoracoscopic direct injection of angiogenic cell precursors into patients with endstage cardiomyopathy.
Cardiomyocyte differentiation of perinatally‑derived mesenchymal stem cells
Coronary heart disease is major cause of mortality worldwide and several risk factors have been shown to play a role in its pathogenesis, including smoking, obesity, hypertension and hypercholesterolemia.
Mesenchymal stem cell secreted platelet derived growth factor exerts a pro-migratory effect on resident Cardiac Atrial appendage Stem Cells
Mesenchymal stem cells (MSCs) modulate cardiac healing after myocardial injury through the release of paracrine factors, but the exact mechanisms are still unknown. One possible mechanism is through mobilization of endogenous cardiac stem cells (CSCs).
Stem Cell Treatment of the Heart
Stem cells are multipotent, undifferentiated cells capable of multiplication and differentiation. Preliminary experimental evidence suggests that stem cells derived from embryonic or adult tissues (especially bone marrow) may develop into myocardial cells.
Immunomodulation
Mesenchymal stem cells and immunomodulation: current status and future prospects
The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.
Human mesenchymal stem cells modulate allogeneic immune cell responses
Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus-host disease (GVHD) during allogeneic transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immunomodulatory functions of human MSCs (hMSCs) by coculturing them with purified subpopulations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [TH1] and TH2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DCs type 1 (DC1) to decrease tumor necrosis factor α (TNF-α) secretion and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused TH1 cells to decrease interferon γ (IFN-γ) and caused the TH2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (TRegs) present; and hMSCs decreased secretion of IFN-γ from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2 (PGE2) in co-cultures, and inhibitors of PGE2 production mitigated hMSC-mediated immune modulation. These data offer insight into the interactions between allogeneic MSCs and immune cells and provide mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation. (Blood. 2005;105:1815-1822)
Immunomodulation by Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are pluripotent stromal cells that have the potential to give rise to cells of diverse lineages. Interestingly, MSCs can be found in virtually all postnatal tissues. The main criteria currently used to characterize and identify these cells are the capacity for self-renewal and differentiation into tissues of mesodermal origin, combined with a lack in expression of certain hematopoietic molecules.
Kidney Diseases
Stem cell-based treatment of kidney diseases
Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases.
Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease: A Review of the Studies Using Syngeneic, Autologous, Allogeneic, and Xenogeneic Cells
Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus (DM) and comprises multifactorial pathophysiologic mechanisms. Despite current treatment, around 30-40% of individuals with type 1 and type 2 DM (DM1 and DM2) have progressive DKD, which is the most common cause of end-stage chronic kidney disease worldwide. Mesenchymal stem cell- (MSC-) based therapy has important biological and therapeutic implications for curtailing DKD progression.
Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models
Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties
Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases
Kidney diseases pose a threat to human health due to their rising incidence and fatality rate. In preclinical and clinical studies, it has been acknowledged that mesenchymal stem cells (MSCs) are effective and safe when used to treat kidney diseases. MSCs play their role mainly by secreting trophic factors and delivering extracellular vesicles (EVs). The genetic materials and proteins contained in the MSC-derived EVs (MSC-EVs), as an important means of cellular communication
Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease
Kidney disease can be either acute kidney injury (AKI) or chronic kidney disease (CKD) and it can lead to the development of functional organ failure. Mesenchymal stem cells (MSCs) are derived from a diverse range of human tissues. They are multipotent and have immunomodulatory effects to assist in the recovery from tissue injury and the inhibition of inflammation. Numerous studies have investigated the feasibility, safety, and efficacy of MSC-based therapies for kidney disease.
Stem cells: a potential treatment option for kidney diseases
The prevalence of kidney diseases is emerging as a public health problem. Stem cells (SCs), currently considered as a promising tool for therapeutic application, have aroused considerable interest and expectations. With self-renewal capabilities and great potential for proliferation and differentiation, stem cell therapy opens new avenues for the development of renal function and structural repair in kidney diseases. Mounting evidence suggests that stem cells exert a therapeutic effect mainly by replacing damaged tissues and paracrine pathways.
Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy disease characterized by progressive formation and enlargement of cysts in multiple organs. The kidneys are particularly affected and patients may eventually develop end-stage renal disease (ESRD). We hypothesize that bone marrow mesenchymal stromal cells (BMMSCs) are renotropic and may improve kidney function via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. In this study, we aim to assess the safety and tolerability of a BMMSC infusion in ADPKD patients.
Stem/progenitor cell in kidney: characteristics, homing, coordination, and maintenance
Renal failure has a high prevalence and is becoming a public health problem worldwide. However, the renal replacement therapies such as dialysis are not yet satisfactory for its multiple complications. While stem/progenitor cell-mediated tissue repair and regenerative medicine show there is light at the end of tunnel. Hence, a better understanding of the characteristics of stem/progenitor cells in kidney and their homing capacity would greatly promote the development of stem cell research and therapy in the kidney field and open a new route to explore new strategies of kidney protection. In this review, we generally summarize the main stem/progenitor cells derived from kidney in situ or originating from the circulation, especially bone marrow. We also elaborate on the kidney-specific microenvironment that allows stem/progenitor cell growth and chemotaxis, and comment on their interaction. Finally, we highlight potential strategies for improving the therapeutic effects of stem/progenitor cell-based therapy. Our review provides important clues to better understand and control the growth of stem cells in kidneys and develop new therapeutic strategies.
Mesenchymal stem cell treatment for chronic renal failure
Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Despite advances in renal replacement therapies and organ transplantation, poor quality of life for dialysis patients and long transplant waiting lists remain major concerns for nephrologists treating this condition.
Stem cell options for kidney disease
Chronic kidney disease (CKD) is increasing at the rate of 6-8% per annum in the US alone. At present, dialysis and transplantation remain the only treatment options. However, there is hope that stem cells and regenerative medicine may provide additional regenerative options for kidney disease.
Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury
Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are particularly attractive cells for cellular and gene therapy in acute kidney injury (AKI). Adenovirus-mediated gene therapy has been limited by immune reaction and target genes selection.
Liver Disease
Stem Cell-Based Therapies for Liver Diseases: An Overview and Update
Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases.
Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases
Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end‐stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo.
Progress in mesenchymal stem cell–based therapy for acute liver failure
Acute liver failure is a life-threatening clinical syndrome characterized by rapid development of hepatocellular necrosis leading to high mortality and resource costs. Numerous treatment strategies for acute liver failure simply prevent complications and decelerate disease progression. The only curative treatment for acute liver failure is liver transplantation, but there are many restrictions on the application of liver transplantation. In recent years, a growing number of studies have shown that stem cells can effectively treat acute liver failure. Several types of stem cells have been used to study liver diseases; mesenchymal stem cells are most commonly used because they are easy to obtain and present no ethical problems. The aims of this article are to review the current knowledge regarding therapeutic mechanisms of mesenchymal stem cells in acute liver failure, to discuss recent advancements in preclinical and clinical studies in the treatment of mesenchymal stem cells, and to summarize the methodological improvement of mesenchymal stem cell transplantation in treating liver failure.
Stem cell transplantation for treating liver diseases: progress and remaining challenges
With the development of regenerative medicine, various stem cells are increasingly considered for treating liver diseases. Various stem cells have been reported to play an essential role in liver recovery, and studies have verified the preliminary effectiveness and safety of these therapies. Stem cell-based therapies will emerge as an effective treatment strategy for liver diseases. Thus, the research progress and challenges to the related stem cells were reviewed, namely the classification of stem cells, cell culture, transplantation, cell tracing in the body, therapies for various liver diseases.
Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis: A systematic review of in vivo studies
Although multiple drugs are accessible for recovering liver function in patients, none are considered efficient. Liver transplantation is the mainstay therapy for end-stage liver fibrosis. However, the worldwide shortage of healthy liver donors, organ rejection, complex surgery, and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases. Mesenchymal stem cell (MSC) therapy is an emerging alternative method for treating patients with liver fibrosis. However, many aspects of this therapy remain unclear, such as the efficiency compared to conventional treatment, the ideal MSC sources, and the most effective way to use it.
Systematic review: the effects of autologous stem cell therapy for patients with liver disease
As morbidity and mortality from liver disease continues to rise, new strategies are necessary. Liver transplantation is not only an expensive resource committing the patient to lifelong immunosuppression but also suitable donor organs are in short supply. Against this background, autologous stem cell therapy has emerged as a potential treatment option.
Stem cell therapy in chronic liver disease
Purpose of review: To provide an overview of the current status of liver regeneration therapies for liver cirrhosis and future prospects.
Recent advances in liver stem cell therapy
Purpose of review: Patients with liver cirrhosis often require liver transplantation, which remains the only effective treatment of the end-stage cirrhosis.
The use of stem cells in liver disease
Purpose of review: Cell transplantation to restore liver function as an alternative to whole liver transplantation has thus far not been successful in humans.
Lungs Disease
Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell
Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis.
Stem cell treatment for chronic lung diseases
Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden.
Stem cell therapy: the great promise in lung disease
Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions,
Erectile Dysfunction
Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis
Stem cell is considered a potential therapy for treating erectile dysfunction (ED), including diabetic mellitus erectile dysfunction (DMED), which was investigated in some preclinical studies. Several trials introduced stem cell into clinical practice, but divergences emerged.
Safety and Efficacy of 2 Intracavernous Injections of Allogeneic Wharton's Jelly-Derived Mesenchymal Stem Cells in Diabetic Patients with Erectile Dysfunction: Phase 1/2 Clinical Trial
Background and objectives: Stem cell therapy is a novel treatment with regenerative ability that can treat erectile dysfunction (ED). This phase 1/2 clinical trial (NCT02945449) using 2 consecutive intracavernous (IC) injections of allogeneic Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) was studied for the first time in the treatment of diabetic patients with ED.
Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial
Background aims: The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM).
Research Advances in Stem Cell Therapy for Erectile Dysfunction
Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie’s disease, smoking, and psychological disorders.
Male Infertility
Stem Cell Therapy for Male Infertility: A Review
Infertility affects 15% of couples in reproductive age world-wide and male factor is solely responsible in about 50% of the cases and contributory in 30-40% of cases. Spermatogonial stem cells (SSCs) are small self-renewing cells found in the basal compartment of seminiferous tubules where they form the foundation of spermatogenesis and are required for the continuous production of sperm
Idiopathic Pulmonary Fibrosis
Stem Cell and Idiopathic Pulmonary Fibrosis: Mechanisms and Treatment
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease resulting from multiplex causes. Evidence indicates that stem/progenitor cells might play a key role in IPF pathogenesis and repair, which may provide some novel potential strategies for the future treatment of IPF.
Cell-based therapies for the treatment of idiopathic pulmonary fibrosis (IPF) disease
During the last few decades, cell-based therapies have shown great potential to treat patients with lung diseases. It has been proposed that the administration of cells into an injured lung could be considered as a therapeutic method to repair and replace lost lung tissue.
Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis is a progressive fibrosing disorder for which there is no cure and no pharmacological treatment capable of increasing in a meaningful way the survival rate. Lung transplantation remains the only possible treatment for patients with advanced disease, although the increase in 5-year survival is only 45 %.
Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER)
Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition.
Lupus
Allogeneic Mesenchymal Stem Cell Transplantation in Severe and Refractory Systemic Lupus Erythematosus: 4 Years of Experience
Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow-derived MSCs from both SLE patients and lupus-prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled. Allogeneic bone marrow or umbilical cord-derived MSCs were harvested and infused intravenously (1 × 106 cells/kg of body weight). Primary outcomes were rates of survival, disease remission and relapse, as well as transplantation-related adverse events.
Additive Therapeutic Effects of Mesenchymal Stem Cells and IL-37 for Systemic Lupus Erythematosus
Although mesenchymal stem cells might have potential for treating SLE, their immunoregulatory plasticity renders their therapeutic effects unpredictable. The authors genetically modified mesenchymal stem cells to overexpress IL-37—a protein with immunosuppressive activity—and assessed the modified cells’ effects on immune suppression in vitro, as well as the effects of transplanting such cells into a mouse model of SLE. Mice transplanted with IL-37–overexpressing cells displayed improved survival and reduced signs of SLE compared with controls. Expression of IL-37 by mesenchymal stem cells can maintain higher serum levels of IL-37, and these cells had prolonged survival after transplantation, perhaps through IL-37 suppressing the inflammatory microenvironment. The additive therapeutic effects of this approach might offer a way to enhance the stability and effectiveness of mesenchymal stem cells in treating SLE.
Mesenchymal stem cell therapy induces FLT3L and CD1c+ dendritic cells in systemic lupus erythematosus patients
Allogeneic mesenchymal stem cells (MSCs) exhibit immunoregulatory function in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain incompletely understood. Here we show that the number of peripheral tolerogenic CD1c+ dendritic cells (DCs) and the levels of serum FLT3L are significantly decreased in SLE patients especially with lupus nephritis, compared to healthy controls. Transplantation of allogeneic umbilical cord-derived MSCs (UC-MSCs) significantly up-regulates peripheral blood CD1c+DCs and serum FLT3L. Mechanistically, UC-MSCs express FLT3L that binds to FLT3 on CD1c+DCs to promote the proliferation and inhibit the apoptosis of tolerogenic CD1c+DCs. Conversely, reduction of FLT3L with small interfering RNA in MSCs abolishes the up-regulation of tolerogenic CD1c+DCs in lupus patients treated with MSCs. Interferon-γ induces FLT3L expression in UC-MSCs through JAK/STAT signaling pathway. Thus, allogeneic MSCs might suppress inflammation in lupus through up-regulating tolerogenic DCs.
Allogeneic Mesenchymal Stem Cell Transplantation in Severe and Refractory Systemic Lupus Erythematosus: 4 Years of Experience
Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow-derived MSCs from both SLE patients and lupus-prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled. Allogeneic bone marrow or umbilical cord-derived MSCs were harvested and infused intravenously (1 × 106 cells/kg of body weight). Primary outcomes were rates of survival, disease remission and relapse, as well as transplantation-related adverse events.
Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study
In our present single-center pilot study, umbilical cord (UC)–derived mesenchymal stem cells (MSCs) had a good safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE). The present multicenter clinical trial was undertaken to assess the safety and efficacy of allogeneic UC MSC transplantation (MSCT) in patients with active and refractory SLE.
Systematic review: the effects of autologous stem cell therapy for patients with liver disease
As morbidity and mortality from liver disease continues to rise, new strategies are necessary. Liver transplantation is not only an expensive resource committing the patient to lifelong immunosuppression but also suitable donor organs are in short supply. Against this background, autologous stem cell therapy has emerged as a potential treatment option.
Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear.
An Overview of the Safety, Efficiency, and Signal Pathways of Stem Cell Therapy for Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and tissues. Mesenchymal stem cells (MSCs) are considered a good source for autoimmune disease and hematological disease therapy.
Stem Cell Therapy Shows Early Promise for the Treatment of Lupus
A newly published study reviewing the current body of scientific evidence on the safety and efficacy of stem cell therapy to treat rheumatic disease highlights the potential benefits of mesenchymal stromal cells (MSCs) – a type of stem cell – for the treatment of lupus.
Lyme Disease
Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease
Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease
Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells
The purpose of this study was to evaluate the longitudinal changes in brain perfusion in patients with Lyme disease treated with human embryonic stem cells.
Lyme disease: diagnosis and management
Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual numbers of cases are increasing and it appears that the distribution across the UK is widening;
Improvement of common variable immunodeficiency using embryonic stem cell therapy in a patient with lyme disease: a clinical case report
Bone marrow transplantation and stem cell therapies have been used for the treatment of common variable immunodeficiency (CVID) and other life‐threatening medical disorders. This is the first known case report in the medical literature describing improvement of both Lyme disease and CVID with human embryonic stem cell therapy.
Hip Pain
Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: A case study
This is a case report of a 64-year-old white male with a 20 year history of unilateral hip pain that had become debilitating over the last several years. On intake, Harris hip score was rated as: Pain subscale = 10, Function subscale = 32, Deformity subscale = 4, Motions subscale = 4.775 with a total score of 50.8 out of 100.
Efficacy and Safety of Bone Marrow Concentrate for Osteoarthritis of the Hip; Treatment Registry Results for 196 Patients
We investigated the efficacy and safety of autologous bone marrow concentrate (BMC) for the treatment of symptomatic hip osteoarthritis. Methods: Treatment registry data for 216 hips treated among 196 patients who underwent a BMC procedure for hip osteoarthritis (OA) were analyzed. Data regarding adverse events (AEs)
Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer
This is a case report of a 64-year-old white male with a 20 year history of unilateral hip pain that had become debilitating over the last several years. On intake, Harris hip score was rated as: Pain subscale = 10, Function subscale = 32, Deformity subscale = 4, Motions subscale = 4.775 with a total score of 50.8 out of 100.
Ankylosing Spondylitis
Mesenchymal stem cells provide novel insights into ankylosing spondylitis
Ankylosing spondylitis (AS), also known as Bechterew’s disease or Marie–Strümpell disease, is an inflammatory disease primarily involving the joints of the spine and pelvis [1]. The cause is unknown; however, genetic factors, environmental triggers, and autoimmunity are all strongly implicated.
Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approach
nkylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis.
Enhanced osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis
The mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture environment.
Multiple Sclerosis
The potential use of mesenchymal stem cells for the treatment of multiple sclerosis
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). In attempt to identify an appropriate treatment for improving the neurological symptoms and remyelination process, autologous and allogenic transplantation of mesenchymal stem cells (MSCs) have been introduced as an effective therapeutic strategy in MS. MSCs are a heterogeneous subset of pluripotent non-hematopoietic stromal cells that are isolated from bone marrow, adipose tissue, placenta and other sources. MSCs have considerable therapeutic effects due to their ability in differentiation, migration, immune-modulation and neuroregeneration. To date, numerous experimental and clinical studies demonstrated that MSCs therapy improves the CNS repair and modulates functional neurological symptoms. Here, we provided an overview of the current knowledge about the clinical applications of MSCs in MS. Furthermore, the major challenges and risks of MSCs therapy in MS patients have been elucidated.
Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR),
The Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells as a Novel Cellular Therapy for Multiple Sclerosis
Multiple sclerosis (MS) is a complex disease of neurological disability, affecting more than 300 out of every 1 million people in the world. The purpose of the study was to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in MS patients. Twenty-three patients were enrolled in this study, and 13 of them were given hUC-MSC therapy at the same time as anti-inflammatory treatment, whereas the control patients received the anti-inflammatory treatment only.
Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Nowadays, available therapies for MS can help to manage MS course and symptoms, but new therapeutic approaches are required. Stem cell therapy using mesenchymal stem cells (MSCs) appeared promising in different neurodegenerative conditions, thanks to their beneficial capacities, including the immunomodulation ability, and to their secretome. The secretome is represented by growth factors, cytokines, and extracellular vesicles (EVs) released by MSCs. In this review
Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC) and induced pluripotent stem cell (iPSCs) derived precursor cells can modulate the autoimmune response in the central nervous system (CNS) and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.
Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis
Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions.
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis
Multiple sclerosis (MS) is a multifocal inflammatory disease that involves the central nervous system and associated with limbs paralysis and serious problems in sensation, limbs, visual and sphincter. This disease is a result of autoimmune mechanism in which autoantibodies target the self-myelin antigens and cause demyelination. Because of the myelin dysfunction, MS is clinically identified with neurological disabilities. Furthermore, it can be entered into the progressive phase because of irreversible neurodegeneration and axons damage. Unfortunately, there is no effective therapeutic method for this disease and current medications have been focused on amelioration of symptoms and chronic inflammation. Although current immunotherapies ameliorate the reactivity of autoimmune anti-myelin and MS relapse rate, there is no approved method for improvement of the disease progression and repairing of the damaged myelin. Therefore, finding an appropriate clinical treatment for improvement of neurological damages in MS patients is essential.
IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year Follow-Up Study
Stem cell transplantation is emerging as a potential therapeutic strategy in several autoimmune diseases. However, the safety and feasibility of long-term combined intravenous (IV) and intrathecal (IT) administration of hUC-MSCs in relapse remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO) is largely unknown.
Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study
More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis.
Stem cell-based therapies for multiple sclerosis: recent advances in animal models and human clinical trials
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS, widely regarded to be autoimmune in nature, and a leading cause of disability among adults aged 20–40 years. Most patients present with a relapsing remitting profile, in which inflammatory flare-ups are interspersed with periods of baseline function.
Use of stem cells for the treatment of multiple sclerosis
The reported evidence of neurodegeneration in multiple sclerosis (MS) may explain the lack of efficacy of the currently used immunomodulating modalities and the irreversible axonal damage, which results in accumulating disability. To date, efforts for neuroprotective treatments have not been successful in clinical studies in other CNS diseases. Therefore, for MS
The role of stem cell therapy in multiple sclerosis: An overview of the current status of the clinical studies
The complexity of multiple sclerosis (MS) and the incompetence of a large number of promised treatments for MS urge us to plan new and more effective therapeutic approaches that aim to suppress ongoing autoimmune responses and induction of local endogenous regeneration.
Parkinson’s Disease
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Cell repair/replacing strategies for neurodegenerative diseases such as Parkinson’s disease depend on well-characterized dopaminergic neuronal candidates that are healthy and show promising effect on the rejuvenation of degenerated area of the brain. Therefore, it is imperative to develop innovative therapeutic strategies that replace damaged neurons with new/functional dopaminergic neurons. Although several research groups have reported the generation of neural precursors/neurons from human/ mouse embryonic stem cells and mesenchymal stem cells, the latter is considered to be an attractive therapeutic candidate because of its high capacity for self-renewable, no adverse effect to allogeneic versus autologous transplants, high ethical acceptance and no teratoma formation.
Cell replacement therapy for Parkinson's disease: how close are we to the clinic?
Cell replacement therapy (CRT) offers great promise as the future of regenerative medicine in Parkinson´s disease (PD). Three decades of experiments have accumulated a wealth of knowledge regarding the replacement of dying neurons by new and healthy dopaminergic neurons transplanted into the brains of animal models and affected patients
Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration
Neurodegenerative diseases include a variety of pathologies such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and so forth, which share many common characteristics such as oxidative stress, glycation, abnormal protein deposition, inflammation, and progressive neuronal loss. The last century has witnessed significant research to identify mechanisms and risk factors contributing to the complex etiopathogenesis of neurodegenerative diseases, such as genetic, vascular/metabolic, and lifestyle-related factors, which often co-occur and interact with each other. Apart from several environmental or genetic factors, in recent years, much evidence hints that impairment in redox homeostasis is a common mechanism in different neurological diseases.
Treatment of Parkinson’s Disease through Personalized Medicine and Induced Pluripotent Stem Cells
Parkinson’s Disease (PD) is an intractable disease resulting in localized neurodegeneration of dopaminergic neurons of the substantia nigra pars compacta. Many current therapies of PD can only address the symptoms and not the underlying neurodegeneration of PD. To better understand the pathophysiological condition, researchers continue to seek models that mirror PD’s phenotypic manifestations as closely as possible. Recent advances in the field of cellular reprogramming and personalized medicine now allow for previously unattainable cell therapies and patient-specific modeling of PD using induced pluripotent stem cells (iPSCs). iPSCs can be selectively differentiated into a dopaminergic neuron fate naturally susceptible to neurodegeneration. In iPSC models, unlike other artificially-induced models, endogenous cellular machinery and transcriptional feedback are preserved, a fundamental step in accurately modeling this genetically complex disease.
Mesenchymal stem cell therapy in Parkinson's disease animal models
Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, and as a consequence, by decreased dopamine levels in the striatum. Currently available therapies are not able to stop or reverse the progression of the disease. A novel therapeutic approach is based on cell therapy with stem cells, in order to replace degenerated neurons. Among stem cells, mesenchymal stem cells seemed the most promising thanks to their capacities to differentiate toward dopaminergic neurons and to release neurotrophic factors.
Pluripotent Stem Cell-based therapy for Parkinson’s disease: current status and future prospects
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease. Because motor impairments in PD largely result from loss of midbrain dopamine neurons in the substantia nigra pars compacta, PD has long been considered to be one of the most promising target diseases for cell-based therapy.
Stem cell-based approach for the treatment of Parkinson's disease
Parkinson’s disease (PD) is the second most common neurodegenerative brain disorder which is around 1.5 times more common in men than in women. Currently, drug medications, surgery, and lifestyle changes are common approaches to PD, while all of them focused on reducing the symptoms.
Stem cell-based therapy for Parkinson's disease
Motor dysfunctions in Parkinson’s disease are considered to be primarily due to the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Pharmacological therapies based on the principle of dopamine replacement are extremely valuable, but suffer from two main drawbacks: troubling side effects (e.g. dyskinesia) and loss of efficacy with disease progression.
Stem cells and the treatment of Parkinson's disease
Progress in Parkinson’s disease (PD) research has been hampered by the lack of an appropriate model which exhibits the core pathology seen in the human brain. Recent advances in deriving cells with neuronal phenotypes from patients with neurodegenerative disorders through cellular reprogramming offer a unique tool for disease modelling and may help shed light on the molecular pathogenesis that drives the progression of the disease.
Stem Cell-Based Therapies for Parkinson Disease
Parkinson disease (PD) is a neurological movement disorder resulting primarily from damage to and degeneration of the nigrostriatal dopaminergic pathway. The pathway consists of neural populations in the substantia nigra that project to the striatum of the brain where they release dopamine. Diagnosis of PD is based on the presence of impaired motor features such as asymmetric or unilateral resting tremor, bradykinesia, and rigidity. Nonmotor features including cognitive impairment, sleep disorders, and autonomic dysfunction are also present.
Primary Biliary Cirrhosis
Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy
This study was designed to assess the safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) in the treatment of rheumatoid arthritis (RA). In this ongoing cohort, 172 patients with active RA who had inadequate responses to traditional medication were enrolled. Patients were divided into two groups for different treatment: disease-modifying anti-rheumatic drugs (DMARDs) plus medium without UC-MSCs, or DMARDs plus UC-MSCs group (4×10(7) cells per time) via intravenous injection. Adverse events and the clinical information were recorded.
Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA.
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study
The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.
Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis
Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.
Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?
The pathogenesis of the autoimmune rheumatological diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is complex with the involvement of several immune cell populations spanning both innate and adaptive immunity including different T-lymphocyte subsets and monocyte/macrophage lineage cells. Despite therapeutic advances in RA and SLE, some patients have persistent and stubbornly refractory disease. Herein, we discuss stromal cells’ dual role, including multipotent mesenchymal stromal cells (MSCs) also used to be known as mesenchymal stem cells as potential protagonists in RA and SLE pathology and as potential therapeutic vehicles. Joint MSCs from different niches may exhibit prominent pro-inflammatory effects in experimental RA models directly contributing to cartilage damage. These stromal cells may also be key regulators of the immune system in SLE. Despite these pro-inflammatory roles, MSCs may be immunomodulatory and have potential therapeutic value to modulate immune responses favorably in these autoimmune conditions. In this review, the complex role and interactions between MSCs and the haematopoietically derived immune cells in RA and SLE are discussed.
Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis
Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated.
Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis
Ursodeoxycholic acid (UDCA) treatment is an effective medical therapy for patients with primary biliary cirrhosis (PBC); however, 40% of PBC patients show an incomplete response to the UDCA therapy. This study aimed to investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transfusion in PBC patients with an incomplete response to UDCA.
Stroke
Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke
Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis.
Stem Cell Transplantation Therapy for Multifaceted Therapeutic Benefits after Stroke
One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke.
Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles
Ischemic stroke is the third cause of death in the developed countries and the main reason of severe disability. Brain ischemia leads to the production of damage-associated molecular patterns (DAMPs) by neurons and glial cells which results in astrocyte and microglia activation, pro-inflammatory cytokines and chemokines production, blood-brain barrier (BBB) disruption, infiltration of leukocytes from the peripheral blood into the infarcted area, and further exacerbation of tissue damage. However, some immune cells such as microglia or monocytes are capable to change their phenotype to anti-inflammatory, produce anti-inflammatory cytokines, and protect injured nervous tissue. In this situation, therapies, which will modulate the immune response after brain ischemia
Autologous Mesenchymal Stem Cells in Chronic Stroke
Cell transplantation is a ‘hype and hope’ in the current scenario. It is in the early stage of development with promises to restore function in chronic diseases. Mesenchymal stem cell (MSC) transplantation in stroke patients has shown significant improvement by reducing clinical and functional deficits. They are feasible and multipotent and have homing characteristics. This study evaluates the safety, feasibility and efficacy of autologous MSC transplantation in patients with chronic stroke using clinical scores and functional imaging (blood oxygen level-dependent and diffusion tensor imaging techniques).
A Long-Term Follow-Up Study of Intravenous Autologous Mesenchymal Stem Cell Transplantation in Patients With Ischemic Stroke
We previously evaluated the short-term follow-up preliminary data of mesenchymal stem cells (MSCs) transplantation in patients with ischemic stroke. The present study was conducted to evaluate the long-term safety and efficacy of i.v. MSCs transplantation in a larger population. To accomplish this, we performed an open-label, observer-blinded clinical trial of 85 patients with severe middle cerebral artery territory infarct. Patients were randomly allocated to one of two groups, those who received i.v. autologous ex vivo cultured MSCs (MSC group) or those who did not (control group), and followed for up to 5 years. Mortality of any cause, long-term side effects, and new-onset comorbidities were monitored. Of the 52 patients who were finally included in this study, 16 were the MSC group and 36 were the control group.
Efficacy of stem cell-based therapies for stroke
Stroke remains a prevalent disease with limited treatment options. Available treatments offer little in the way of enhancing neurogenesis and recovery. Because of the limitations of available treatments, new therapies for stroke are needed. Stem cell-based therapies for stroke offer promise because of their potential to provide neurorestorative benefits. Stem cell-based therapies aim to promote neurogenesis and replacement of lost neurons or protect surviving neurons in order to improve neurological recovery. The mechanism through which stem cell treatments mediate their therapeutic effect is largely dependent on the type of stem cell and route of administration.
Stem cell therapy in stroke: a review literature
Stroke is an important cause of death in the world and disability world-wide especially in developed countries. Following acute phase of stroke, some procedures and medical treatment such as thrombolytic agents has been recommended; nevertheless many patients have enduring deficits. Thus, there is a realistic need to develop treatment strategies for reducing neurological deficits.
Recent Advances in Cell-Based Therapies for Ischemic Stroke
Stroke is the most prevalent cardiovascular disease worldwide, and is still one of the leading causes of death and disability. Stem cell-based therapy is actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types of cells, including bone marrow mononuclear cells, bone marrow mesenchymal stem cells, dental pulp stem cells, neural stem cells, inducible pluripotent stem cells, and genetically modified stem cells have been found to improve neurological outcomes in animal models of stroke, and there are some ongoing clinical trials assessing their efficacy in humans. In this review, we aim to summarize the recent advances in cell-based therapies to treat stroke.
Traumatic Brain Injury
The neuroprotection of hypoxic adipose tissue-derived mesenchymal stem cells in experimental traumatic brain injury
Traumatic brain injury is one of the leading causes of mortality and morbidity worldwide. At present there is no effective treatment. Previous studies have demonstrated that topical application of adipose tissue-derived mesenchymal stem cells can improve functional recovery in experimental traumatic brain injury. In this study, we evaluated whether hypoxic preconditioned mesenchymal stem cells could enhance the recovery from traumatic brain injury.
Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury
Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long‐term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties
Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain.
Cell-Based therapy for traumatic brain injury
Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality.
Genetically Modified Mesenchymal Stem Cells: The Next Generation of Stem Cell-Based Therapy for TBI
Mesenchymal stem cells (MSCs) are emerging as an attractive approach for restorative medicine in central nervous system (CNS) diseases and injuries, such as traumatic brain injury (TBI), due to their relatively easy derivation and therapeutic effect following transplantation. However, the long-term survival of the grafted cells and therapeutic efficacy need improvement.
Intravenous mesenchymal stem cell therapy for traumatic brain injury
Cell therapy has shown preclinical promise in the treatment of many diseases, and its application is being translated to the clinical arena. Intravenous mesenchymal stem cell (MSC) therapy has been shown to improve functional recovery after traumatic brain injury (TBI). Herein, the authors report on their attempts to reproduce such observations, including detailed characterizations of the MSC
Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae.
Cell therapies for traumatic brain injury
Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease.
Mesenchymal Stem Cells of Dental Origin-Their Potential for Anti-inflammatory and Regenerative Actions in Brain and Gut Damage
Alzheimer’s disease, Parkinson’s disease, traumatic brain and spinal cord injury and neuroinflammatory multiple sclerosis are diverse disorders of the central nervous system. However, they are all characterized by various levels of inappropriate inflammatory/immune response along with tissue destruction. In the gastrointestinal system, inflammatory bowel disease (IBD) is also a consequence of tissue destruction resulting from an uncontrolled inflammation.
Stem Cell Therapy for Cerebral Palsy
Treatment of Cerebral Palsy with Stem Cells: A Report of 17 Cases
Cerebral Palsy (CP) is a disabling condition that affects a child’s life and his/her family irreversibly. It is usually a non-progressive condition but improvement over time is rarely seen. The condition can be due to prenatal hypoxia, metabolic, genetic, infectious, traumatic or other causes. It is therefore a heterogeneous group that results in functional motor disability associated with different degrees of cognitive abnormalities. There are no treatments that can cure or even improve CP and the best available approach aims at functional, social and nutritional supportive care and counseling. In this paper, we report 17 sequential patients with CP treated with intrathecal administration of Bone Marrow Mononuclear Cells (BMMC). All patients had an uneventful post-injection course with 73% of the evaluable patients treated having a good response using the Gross Motor Function Classification System (GMFCS). The average improvement was 1.3 levels on the GMFCS with cognitive improvements as well.
Stem cell treatment and cerebral palsy: Systemic review and meta-analysis
Perinatal complications may result in life-long morbidities, among which cerebral palsy (CP) is the most severe motor disability. Once developed, CP is a non-progressive disease with a prevalence of 1-2 per 1000 live births in developed countries. It demands an extensive and multidisciplinary care. Therefore, it is a challenge for our health system and a burden for patients and their families. Recently, stem cell therapy emerged as a promising treatment option and raised hope in patients and their families.
The Role of Stem Cells in the Treatment of Cerebral Palsy: A Review
Cerebral palsy (CP) is a neuromuscular disease due to injury in the infant’s brain. The CP disorder causes many neurologic dysfunctions in the patient. Various treatment methods have been used for the management of CP disorder. However, there has been no absolute cure for this condition. Furthermore, some of the procedures which are currently used for relief of symptoms in CP, cause discomfort or side effects in the patient. Recently, stem cell therapy has attracted a huge interest as a new therapeutic method for treatment of CP.
Autologous Stem Cell Therapy for Cerebral Palsy
<span “=””>We describe treatment of Cerebral Palsy with adult stem cells derived from bone marrow and fat of the same patient. Adult stem cells are of two types, the mesenchymal and haemopoietic stem cells which have potential to duplicate, indefinitely produce 50 types of growth factors that repair<span “=””> and regenerate tissues in an epigenetic manner. Every organ has its own stem cells, for example kidney stem cells, liver stem cells,<span “=””> etc. When specialized cells in an organ get damaged, the local stem cells come forward and get differentiated into specialized cells and the tissue damage is replenished. But when the stock of this reserve of local stem cell is over, the organ starts failing.
Neurological Disease
Role of Stem Cells in Treatment of Neurological Disorder
Stem cells or mother or queen of all cells are pleuropotent and have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is alive. When a stem cell divides
Stem cells as promising therapeutic options for neurological disorders
Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells
Stem cells for the treatment of neurological disorders
Many common neurological disorders, such as Parkinson’s disease, stroke and multiple sclerosis, are caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated successfully from stem cells in culture, fueling efforts to develop stem-cell-based transplantation therapies for human patients.
Stem Cell Technology for Neurodegenerative Diseases
Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion on the burden of these diseases on society, emphasizing the need for increased attention towards advancing stem cell therapies.
Muscular Dystrophy
Duchenne muscular dystrophy: current cell therapies
Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed.
Induced Pluripotent Stem Cells for Duchenne Muscular Dystrophy Modeling and Therapy
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, caused by mutation of the DMD gene which encodes the protein dystrophin. This dystrophin defect leads to the progressive degeneration of skeletal and cardiac muscles. Currently, there is no effective therapy for this disorder. However, the technology of cell reprogramming, with subsequent controlled differentiation to skeletal muscle cells or cardiomyocytes, may provide a unique tool for the study, modeling, and treatment of Duchenne muscular dystrophy. In the present review, we describe current methods of induced pluripotent stem cell generation and discuss their implications for the study, modeling, and development of cell-based therapies for Duchenne muscular dystrophy.
Stem cell therapy for muscular dystrophy
Muscular dystrophy is a heterogeneous group of neuromuscular disorders that manifests as progressive muscle weakness, muscle wasting and, in many cases, death. Although there has been enormous progress in the molecular understanding of muscular dystrophy, there is still no cure. There are, however, several different therapeutic options under investigation, including adult-derived stem cell transplantation. Encouraging and pioneering experiments in mouse models for Duchenne’s muscular dystrophy (DMD) demonstrated that myoblasts could be transplanted into dystrophic muscle; these myoblasts repaired a small proportion of damaged myofibres. Subsequent work has been devoted to optimisation of this technique. In doing so, a number of adult-derived stem cells have been isolated, characterised and used in promising animal transplantation experiments. Further research is ongoing, and is clearly necessary to make this therapy a viable treatment option for patients with muscular dystrophy.
Cell therapy strategies and improvements for muscular dystrophy
Understanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this review, we will consider the regenerative potential of embryonic and somatic stem cells and the outcomes achieved on their transplantation into animal models for muscular dystrophy or acute muscle impairment.
The role of stem cells in muscular dystrophies
Muscular dystrophies are heterogeneous neuromuscular disorders of inherited origin, including Duchenne muscular dystrophy (DMD). Cell-based therapies were used to promote muscle regeneration with the hope that the host cells repopulated the muscle and improved muscle function and pathology. Stem cells were preferable for therapeutic applications, due to their capacity of self-renewal and differentiative potential.
Stem cell transplantation for treating Duchenne muscular dystrophy
To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science.
Stem cell therapy for muscular dystrophy
Muscular dystrophy is a heterogeneous group of neuromuscular disorders that manifests as progressive muscle weakness, muscle wasting and, in many cases, death. Although there has been enormous progress in the molecular understanding of muscular dystrophy, there is still no cure.
The role of stem cells in muscular dystrophies
Muscular dystrophies are heterogeneous neuromuscular disorders of inherited origin, including Duchenne muscular dystrophy (DMD). Cell-based therapies were used to promote muscle regeneration with the hope that the host cells repopulated the muscle and improved muscle function and pathology.
Stem cell transplantation for treating Duchenne muscular dystrophy: A Web of Science-based literature analysis
To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science.
Motor Neuron Disease
Stem cell technology for the study and treatment of motor neuron diseases
Amyotrophic lateral sclerosis and spinal muscular atrophy are devastating neurodegenerative diseases that lead to the specific loss of motor neurons. Recently, stem cell technologies have been developed for the investigation and treatment of both diseases. Here we discuss the different stem cells currently being studied for mechanistic discovery and therapeutic development, including embryonic, adult and induced pluripotent stem cells. We also present supporting evidence for the utilization of stem cell technology in the treatment of amyotrophic lateral sclerosis and spinal muscular atrophy, and describe key issues that must be considered for the transition of stem cell therapies for motor neuron diseases from bench to bedside. Finally, we discuss the first-in-human Phase I trial currently underway examining the safety and feasibility of intraspinal stem cell injections in amyotrophic lateral sclerosis patients as a foundation for translating stem cell therapies for various neurological diseases.
The Use of Stem Cells in Motor Neurone Disease (MND)
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, caused by mutation of the DMD gene which encodes the protein dystrophin. This dystrophin defect leads to the progressive degeneration of skeletal and cardiac muscles. Currently, there is no effective therapy for this disorder. However, the technology of cell reprogramming, with subsequent controlled differentiation to skeletal muscle cells or cardiomyocytes, may provide a unique tool for the study, modeling, and treatment of Duchenne muscular dystrophy. In the present review, we describe current methods of induced pluripotent stem cell generation and discuss their implications for the study, modeling, and development of cell-based therapies for Duchenne muscular dystrophy.
Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems. In this review, we focused on the studies involving ALS rodent models and clinical trials in order to understand the potential beneficial effects of MSC transplantation.
Stem Cell Transplantation for Motor Neuron Disease: Current Approaches and Future Perspectives
Motor neuron degeneration leading to muscle atrophy and death is a pathological hallmark of disorders, such as amyotrophic lateral sclerosis or spinal muscular atrophy. No effective treatment is available for these devastating diseases. At present, cell-based therapies targeting motor neuron replacement, support, or as a vehicle for the delivery of neuroprotective molecules are being investigated. Although many challenges and questions remain, the beneficial effects observed following transplantation therapy in animal models of motor neuron disease has sparked hope and a number of clinical trials. Here, we provide a comprehensive review of cell-based therapeutics for motor neuron disorders, with a particular emphasis on amyotrophic lateral sclerosis.
Stem Cell Therapy in Motor Neuron Disease
Motor neuron disease (MND) is an insidious, fatal disorder that progresses with the selective loss of anterior horn cells of the spinal column. Over 150 years since it was first described, various therapeutic approaches have been tested in the quest of a cure but with little success. Current standard therapy only improves lifespan by a few months; palliative care is the only option available for patients. Stem cell therapy is a potent approach for the treatment of this devastating disease. A multitude of vitalizing effects
Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia
Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) – induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells
Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis
Motor neuron degeneration leading to muscle atrophy and death is a pathological hallmark of disorders, such as amyotrophic lateral sclerosis or spinal muscular atrophy. No effective treatment is available for these devastating diseases. At present, cell-based therapies targeting motor neuron replacement, support, or as a vehicle for the delivery of neuroprotective molecules are being investigated. Although many challenges and questions remain, the beneficial effects observed following transplantation therapy in animal models of motor neuron disease has sparked hope and a number of clinical trials. Here, we provide a comprehensive review of cell-based therapeutics for motor neuron disorders, with a particular emphasis on amyotrophic lateral sclerosis.
Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Patients show both motor and extra-motor symptoms. A cure is not available at this time, and the disease leads to death within 3–5 years, mainly due to respiratory failure. Stem cell therapy is arising as a new promising approach for the treatment of neurodegenerative disorders. In particular, mesenchymal stem cells (MSCs) seem the most suitable type of stem cells, thanks to their demonstrated beneficial effects in different experimental models, to the easy availability, and to the lack of ethical problems. In this review, we focused on the studies involving ALS rodent models and clinical trials in order to understand the potential beneficial effects of MSC transplantation.
Neuroprotective Potential of Cell-Based Therapies in ALS: From Bench to Bedside
Motor neurons (MN) degeneration is a main feature of amyotrophic lateral sclerosis (ALS), a neurological disorder with a progressive course. The diagnosis of ALS is essentially a clinical one. Most common symptoms include a gradual neurological deterioration that reflect the impairment and subsequent loss of muscle functions. Up-to-date ALS has no therapy that would prevent or cure a disease. Modern therapeutic strategies comprise of neuroprotective treatment focused on antiglutamatergic, antioxidant, antiapoptotic, and anti-inflammatory molecules.
NurOwn, phase 2, randomized, clinical trial in patients with ALS
To determine the safety and efficacy of mesenchymal stem cell (MSC)-neurotrophic factor (NTF) cells (NurOwn®, autologous bone marrow-derived MSCs, induced to secrete NTFs) delivered by combined intrathecal and intramuscular administration to participants with amyotrophic lateral sclerosis (ALS) in a phase 2 randomized controlled trial.
Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases
Mesenchymal stromal cells are multipotent cells that are being used to treat a variety of medical conditions. Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies. In this review, we discuss the proposed MSC mechanisms of action in neurodegenerative diseases, which include growth factor secretion, exosome secretion, and attenuation of neuroinflammation. We then provide a summary of preclinical and early clinical work on MSC therapies in amyotrophic lateral sclerosis, multiple system atrophy, Parkinson’s disease, and Alzheimer’s disease. Continued rigorous and controlled studies of MSC therapies will be critical in order to establish efficacy and protect patients from possible untoward side effects.
Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy
Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine.
Mesenchymal Stem Cells
Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy
Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine.
Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases
Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.
Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation
In addition to their stem/progenitor properties, mesenchymal stromal cells (MSCs) possess broad immunoregulatory properties that are being investigated for potential clinical application in treating immune-based disorders. An informed view of the scope of this clinical potential will require a clear understanding of the dynamic interplay between MSCs and the innate and adaptive immune systems. In this Review, we outline current insights into the ways in which MSCs sense and control inflammation, highlighting the central role of macrophage polarization. We also draw attention to functional differences seen between vivo and in vitro contexts and between species. Finally, we discuss progress toward clinical application of MSCs, focusing on GvHD as a case study.
Extracellular vesicles derived from Wharton’s Jelly mesenchymal stem cells inhibit the tumor environment via the miR-125b/HIF1α signaling pathway
Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis.
