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One of the most known stem cells are mesenchymal stem cells which can be proven beneficial for regenerative stem cell-based therapies. These cells can do several things because of which they provide promising results to treat various medical conditions. By this article, you will know about mesenchymal stem cells, their common sources, and how they work.

Knowing About Mesenchymal Stem Cells

Stem cells are the best building buddies of our body and can transform into any other types of cells because of a special function. One of those stem cells are mesenchymal stem cells. MSCs is categorized in adult stem cells that have several properties such as self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation. If we talk about MSCs self-renewal properties, then this is categorized as an ability in which they divide and transform into various types of specialized cells.

These cells can be obtained from various tissues within the body such as bone marrow, adipose tissue (fat), umbilical cord tissue, liver, dental pulp, skin, and blood. We will talk about mesenchymal stem cells which can be obtained from upper mentioned tissue through this article.

Clinical Application

As you know, MSCs have several properties such as self-renewable, differentiation, anti-inflammatory, and immunomodulatory by which they can be useful for the treatment of various diseases. Two types of studies that are in-vitro (means studies performed in labs) and in-vivo (means performed in a living organism) provide the support to understand the mechanism, safety, and efficacy of MSC therapy in clinical applications.

MSCs Derived from Adipose Tissue (ADSCs)

Mesenchymal stem cells which are derived from adipose tissue are the cells that can be taken in large numbers. These cells are very active and can be taken with the help of a procedure known as liposuction.

ADSCs are shown to be more effective and better if you derived it from a younger donor rather than an old one. If an older patient undergoes a procedure where their cells are used, then it will create problems for them. Older patients’ cells may not be as good as staying alive in the recipient’s body for a long time. Stem cells taken from fat of younger people grow faster after being transplanted than those from older people. However, even as people age, these cells can still turn into different types of cells. This makes them better than stem cells from bone marrow for certain purposes.

ADSCs can still turn into cells from the middle layer of the body (mesoderm). They’re also known for not causing much of an immune response and for being able to change how the immune system works. Less than 1 out of 100 of them showed the HLA-DR protein on their surface, which helps suppress the immune system. This makes them useful for treating immune disorders that don’t respond to regular treatments, and for transplants between people who aren’t related.

Many people agree that ADSCs can help treat lots of different health problems. Moreover, ADSCs can be a good option for the majority of orthopedic procedures.  Applications such as arthritis, knee discomfort, spinal cord injuries, localized joint inflammation, and other musculoskeletal problems are frequently seen.

Still, there are still several difficulties in using ADSCs in a therapeutic context. These difficulties include restricted differentiation capacities, protocol standardization, and proliferative restrictions related to cell age.

Bone Marrow-Derived MSCs (BM-MSCs)

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are from the multipotent adult stem cells category which have various properties such as self-renewable, differentiation, and immunomodulatory and can be used to treat various medical conditions and diseases.

Research conducted both in vitro and in vivo have provided evidence for the mechanisms, safety, and effectiveness of BM-MSC therapy in clinical settings. Phase I and II clinical trial numbers are increasing, but they are constrained by subject size restrictions, rules, and guidelines for the manufacture, transportation, and administration of bone marrow-derived mesenchymal stem cells (BMSCs). As a result, therapeutic outcomes and inputs are inconsistent.

Limitations

The extraction of bone marrow is an extremely intrusive and unpleasant surgery that necessitates several days of hospital stay under general anesthesia. Only 0.002% of stromal (stem) cells are BM-MSCs, making them an uncommon population whose isolation is dependent on the patient’s condition and the amount of material taken.

The quantity and quality of these cells reduce with age which is similar to ADSCs. When using an allogeneic (cells from a third party) treatment, BM-MSCs from younger donors are probably more viable. When older individuals undergo autologous procedures, this could become problematic because the recipient’s older cells might not be as well-suited for long-term survival. Chu et al. describe this problem in a 2020 study.

Many diseases can be treated by BM-MSCs and it is proven by various clinical trials and tests. BM-MSCs therapy is currently being used to treat injuries sustained in sports, neurological illnesses, and osteoarthritis.

Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSCs)

The peri-vascular zone of the umbilical cord, Wharton’s jelly, and the cord lining are some of the sources of UC-MSCs. Since the umbilical cord is frequently discarded tissue, it is a rich source of mesenchymal stromal cells that can be collected non-invasively.

These cells come with various abilities and one of those is differentiation. UC-MSCs have the ability to divide themselves into different types of cells with a heavy proliferation rate of the three types of stem cells (adipose, bone marrow, cord tissue).

Like MSCs produced from bone marrow and adipose tissue, UC-MSCs are known to secrete chemokines, cytokines, and growth factors that enhance various cell healing pathways. All of these roles support MSCs’ immunomodulatory and anti-inflammatory capabilities.

Non-Invasive Cell Product

UC-MSC harvesting is a non-invasive process because the patient does not need to be extracted. The MSCs are extracted straight from a section of a human umbilical cord that has been ethically donated. Because UC-MSCs proliferate more efficiently in vitro than BMSCs and ASCs do, it is possible to obtain higher cell numbers with more efficiency. Research has revealed that UC-MSCs exhibited upregulation (an increase in the number of receptors) of genes linked to cell proliferation (EGF), the PI3K-NFkB signaling pathway (TEK), and neurogenesis (RTN1, NPPB, and NRP2).

Comparison Between BMSCs, ADSCs, and UC-MSCs

Characteristics BMSCs ADSCs UC-MSCs
Process of harvesting Invasive Invasive Non-invasive
Age effect Decline of quantity and quality Decline of quantity and quality Unaffected
Potency Lower Lower Higher
Cell renewal capabilities Lower proliferative potential Lower proliferative potential Higher proliferative potential
Expression of embryonic markers Lower Lower Higher
Properties (immune modulatory) Good Good Good
Rejection of allogeneic cell No No No
Issues No No No
Tumorigenicity risk No No No

Mechanism of Mesenchymal Stem Cells in the Body

Mesenchymal stem cells use its properties which are self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation to improve the functioning of the body tissue. The self-renewal property of MSCs can be beneficial to treat various medical conditions and disorders because they can divide themselves into several specialized types of cells. Since mesenchymal stem cells are adult stem cells and are not derived from embryonic material, they do not raise any ethical issues.

Immunomodulatory

Mesenchymal stem cells (MSCs) help control the immune system. They can boost the immune response when it is too weak and reduce inflammation when it is too strong. These cells are the best option to fight with autoimmune disorders which may destroy your own immune system. A 2013 study by Bernardo et al. claims that MSCs induce an immune-suppressive response to reduce inflammation and support tissue homeostasis in response to exposure to high concentrations of pro-inflammatory signals (cytokines).

Anti-inflammatory 

Inflammation is how the immune system reacts to protect the body from harmful things and helps in healing and repairing the body. On the other hand, when inflammation is dysregulated, the body may suffer. Long-term immunological dysregulation can result in a number of autoimmune diseases, including lupus, multiple sclerosis, type 1 diabetes, and inflammatory bowel disease.

How Do MSCs Decrease Inflammation?

According to a Gugjoo report from 2020, “MSCs from different sources reduce inflammation by decreasing production of tumor necrosis factor-α (TNF-α) and Interferon-γ (IFN-γ) and increasing Prostaglandin (PGE2) and Interleukin-6 (IL-6) secretion.”

MSCs Secretome and Extracellular Vesicles

The healing effects of mesenchymal stem cells are not just because they can turn into different types of cells and replace damaged tissues. They also help by releasing substances that assist in healing through nearby cell signaling.

The MSC secretome is a collection of active substances that are released into the body. These include proteins that affect cell communication (cytokines), proteins that help cells grow (growth factors), small particles released by cells (extracellular vesicles), proteins that support nerve cells (neurotrophins), and other soluble proteins, fats (lipids), and genetic material (nucleic acids).

The substances released by cells, known as secretomes, are crucial in controlling many body functions. They are becoming more important as possible indicators of disease and targets for treatment.

A 2016 study by Arutyunyan and colleagues found that UC-MSCs (stem cells from umbilical cords) release more helpful proteins for nerve growth, like bFGF, NGF, NT3, NT4, and GDNF, than stem cells from bone marrow (BM-MSCs) or fat tissue (AT-MSCs).

UC-MSCs release a lot more important substances like G-CSF, GM-CSF, LIF, IL-1α, IL-6, IL-8, and IL-11, which help with cell growth and immune system function, compared to BM-MSCs.

How MSCs Locate Tissues in Need?

One big advantage of mesenchymal stem cells is that they can find and go to specific areas in your body that need help because they have a natural ability to do so. These cells are injected to go to the bloodstream and then they leave the blood and move to the part which is injured or damaged.

A study conducted by Ulah in 2019 has shown that there are many steps which include the control of systemic homing processes by specific molecules to interact with each other. “The process of systemic homing can be split into five steps: tethering and rolling, activation, arrest, transmigration or diapedesis, and migration”.

Differentiation

Mesenchymal stem cells have the ability to differentiate into different types of cells because these are multipotent stem cells and have  self-renew properties. In simple words, MSCs can divide themselves and become a variety of cell types such as adipose tissue, cartilage, muscle, tendon/ligament, bone, neurons, and hepatocytes.

According to a 2016 study conducted by Almalki et al. –  “The differentiation of MSCs into specific mature cell types is controlled by various cytokines, growth factors, extracellular matrix molecules, and transcription factors (TFs).”

Mesenchymal stem cells help fix and grow tissues. They keep the body balanced and working well, adjust to changes in metabolism or environment, and repair damaged tissues.

The functions of mesenchymal stem cells are being studied in great detail. Researchers can learn about their many properties, including as immunomodulatory, anti-inflammatory, self-renewal, signaling, and differentiation, through studies and clinical trials. MSCs can be employed as a professional medical instrument to treat various medical illnesses or disorders because of these qualities.

Research suggests that mesenchymal stem cells (MSCs) from umbilical cord tissue (UC-MSCs) might be more powerful than MSCs from other sources, which could make them more effective for medical treatments.

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