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Stem cells are undifferentiated cells which can implement a multiplicity of regenerative functions in the human body. They can for example generate or replace a diversity of cells through differentiation, adjust the immune system and stimulate other cells in their natural environment. Stem cells are present in all human beings from embryo/fetus development (embryonic stem cells) and throughout any individual’s entire lifespan until death (Adult Stem Cells). It is vital to note that embryonic stem cells (ESC) and Adult Stem Cells are two very different groupings of stem cells having varied properties. In any individual, after birth, cell replacement and regeneration happen in two contexts: regeneration of naturally dying cells (apoptosis) and in response to peripheral injury (caused by factors such as traumatic injury, infection, cancer, infarction, toxins, swelling, etc.). The stem cells involved in that renewal process are the Adult Stem Cells (also called Somatic Stem Cells).

Adult Stem Cells and Embryonic Stem Cells

Embryonic stem cells are present in the internal cell mass of the blast cyst, a mainly hollow ball of cells that, in the human, forms three to five days after an egg cell is fertilized by a sperm. In normal development, the cells inside the internal cell mass will yield the more specialized cells that give rise to the whole body—all of our tissues and organs. Embryonic stem cells are pluripotent, meaning they can give rise to every cell category in the fully formed body, but not the placenta and umbilical cord. Adult stem cells (also referred somatic stem cells) are more specialized than embryonic stem cells. Typically, these stem cells can generate diverse cell categories for the particular tissue or organ in which they live. There are several different kinds of Adult Stem Cells, that all have their particular regenerative functions. For instance, blood-forming (or hematopoietic) stem cells can give rise to red blood cells, white blood cells and platelets. However, blood-forming stem cells don’t engender liver or lung cells for example, and stem cells in other tissues and organs don’t generate red or white blood cells or platelets. Some tissues and organs within your body encompass small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are misplaced in normal everyday living or in injury.

How do stem cells target injury? – Homing

In stem cell science, the word “homing” designates stem cells’ aptitude to find their destination, or “niche.” During that procedure, impaired or inflamed tissues call for repair by sending out signals, some of which act as signals for stem cells and attract them to the injured tissue. This is a fairly quick process (measured in hours and no longer than 1-2 days).

How do stem cells work for tissue repair? – Direct Differentiation and Paracrine Effect

Once the stem cells have voyaged to the injury site, they might begin their regenerative action by acting via two diverse mechanisms: they might undergo direct differentiation so as to directly replace the injured cells or they might also encourage tissue regeneration through the Paracrine Effect.

What is the paracrine effect?

In stem cell science, it can be defined by the procedure in which the stem cells release factors that act as signals for surrounding cells, and force them to change their behavior to start the regeneration process. During that procedure, stem cells do not contribute to tissue renewal via direct differentiation.

Why is the paracrine effect so important?

In a huge amount of studies about stem cell transplants, researchers observed that injured patient tissues were repaired after stem cell transplant from donor. However, after examining the newly generated tissues it has been detected that donor cells were absent. Scientists were then able to validate that the donor stem cells were secreting factors that prompted the patient’s own cells to repair the tissue themselves. It has been proven that maximum of the regeneration process was accomplished via paracrine signaling and not via direct differentiation. The paracrine mechanism has turned out to be very advantageous. The advantages of having a paracrine effect are now very obvious. The most significant fact is that even though the donor stem cells have a very restricted lifespan, they have a long -long-lasting effect on tissue regeneration, which goes on long after total exhaustion of donor stem cells. Numerous diverse types of stem cell can invoke a paracrine response such as umbilical cord mesenchymal stem cells and umbilical cord blood stem cells.

What can stem cells accomplish via direct differentiation and paracrine effect?

  • Repair impaired tissue: stem cells have the aptitude to activate the quiescent state of stem cells in the human body and have a repair effect on the impaired tissue and organ instigated by the peroxidation and metabolic waste. A balance between free radicals and antioxidants is essential for appropriate physiological function. If free radicals overwhelm the body’s aptitude to regulate them, a condition known as oxidative stress ensues. Free radicals thus unfavorably adjust lipids, proteins, and DNA and elicit numerous human ailments. Stem cells can also intervene the free radical stress to reestablish its normal function.
  • Secrete nutritional factors: Stem cells can promote the tissue multiplying and differentiation within the impaired tissue and reestablish the physiological functions of tissues and organs.
  • Regulate the immune function: Via the secretion of soluble factors and direct contact to regulate immune cells’ proliferation and its activity, stem cells are able to lessen the inflammatory response.
  • Regulate the metabolic function: Using the aptitude of multi-directional differentiation, stem cells can augment the effectiveness of metabolic system and thus quicken the body’s operation and excretion of metabolic waste to encourage the absorption of nutrients, so that maintain the normal physiological function.

Furthermore, studies have specified that the paracrine effect is augmented as the donor cells are attracted to the impaired tissues that need their support. The impaired patient cells are secreting cytokines, regulatory proteins that act as intermediaries to generate an immune response that entice the donor cells. In turn, the donor cells secrete their own cocktail of proteins that stimulate the patient’s stem cells and aid to decrease swelling, promote cell production, and upsurge vascularization and blood flow into the zones that need to heal. Paracrine effect cells can also secrete factors that prevent the death of patient cells because of injury or ailment. A significant third paracrine effect is their aptitude to ‘dampen’ the immune reaction that happens during transplant rejection or during autoimmune disease (1). In this case the cells can be used straight or in combination with other stem cells for therapeutic purposes. For instance, the application of mesenchymal cells accompanied by blood stem cells during a bone marrow transplant seems to lessen graft versus host disease (2).

A benefit of using cells, versus medicine, to promote regeneration is that transplanted cells will respond to their environment and discharge the factors as they are required and in the most apt concentration. The cells can be thought of as ‘drug factories’ that adapt as the tissue is refurbished. Preclinical studies have verified the efficiency of mesenchymal cells and cord blood cells for the treatment of neural, heart, kidney and muscle based syndromes. There have been some resounding studies on the neuroprotective effect of cord blood cells.