Stem cells are undifferentiated cells which can perform a variety of regenerative functions in the human body. They can for instance generate or replace a variety of cells through differentiation, regulate the immune system and stimulate other cells in their natural environment.
Stem cells are present in all human beings from embryo/fœtus development (embryonic stem cells) and throughout any individual whole lifespan until death (Adult Stem Cells). There are 5 general types of stem cells, defined by both their origin and their ability to generate new cells.
- Totipotent: Also known as the fertilized egg, this cell will develop and become all other cells, creating a human being.
- Pluripotent: These stem cells can differentiate into any other kind of cell, however, they lack the capacity to create an entire organism in the way a totipotent cell can.
- Multipotent: Slightly more limited than pluripotent cells, assigned to a certain range of cell types.
- Oligopotent: These stem cells are similar to multipotent stem cells and are also able to differentiate into a specific range of cell types.
- Unipotent: These stem cells are only able to differentiate into one type of cell.
Embryonic stem cells (ESC) and adult stem cells (ASC) are two very different categories of stem cells having different properties. In any individual after birth, cell replacement and regeneration occur in two contexts: renewal of naturally dying cells (apoptosis) and in response to external injury (caused by factors such as traumatic injury, infection, cancer, infarction, toxins, inflammation, etc.). The stem cells involved in that regeneration process are the adult stem cells (also called somatic stem cells).
Adult Stem Cells and Embryonic Stem Cells
Embryonic stem cells are present the inner cell mass of the blastocyst, 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 inner cell mass will give rise to the more specialized cells that give rise to the entire body—all of our tissues and organs. Embryonic stem cells are pluripotent, which as previously mentioned, means they can give rise to every cell type 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 different cell types for the specific tissue or organ in which they live. There are many different types of adult stem cells, that all have their specific regenerative functions. For example, 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 generate liver or lung cells for instance, 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 contain small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are lost in normal day-to-day living or in injury.
How do Stem Cells target injury? – Homing
In stem cell science, the word “homing” describes stem cells’ ability to find their destination, or “niche.” During that process, damaged or inflamed tissues call for repair by sending out signals, some of which act as cues for stem cells and attract them to the injured tissue. This is a fairly rapid—process (measured in hours and no longer than 1-2 days).
How do Stem Cell work for tissue repair? – Direct Differentiation and Paracrine Effect
Once the stem cells have traveled to the injury site, they may start their regenerative action by acting through two different mechanisms: they may undergo direct differentiation in order to to directly replace the injured cells or they may also promote tissue regeneration through the paracrine effect.
So what is the paracrine effect? In stem cell science, it can be defined by the process in which the stem cells release factors that act as signals for surrounding cells, and force them to change their behavior to initiate the regeneration process. During that process, stem cells do not contribute to tissue renewal through direct differentiation.
Why is the paracrine effect so important?
In a large amount of studies about stem cell transplants, researchers observed that damaged patient tissues were repaired after stem cell transplant from a donor. However, after analyzing the newly generated tissues it has been observed that the donor cells were absent. Scientists were then able to demonstrate that the donor stem cells were secreting factors that triggered the patient’s own cells to repair the tissue themselves. It has been demonstrated that most of the regeneration process was accomplished through paracrine signaling and not through direct differentiation.
The paracrine mechanism has turned out to be very beneficial. The advantages of having a paracrine effect is now very apparent. The most important fact is that even though the donor stem cells have a very limited lifespan, they have a long lasting effect on tissue regeneration, which goes on long after total depletion of donor stem cells.
What can stem cells accomplish through direct differentiation and paracrine effect?
- Repair damaged tissue: stem cells have the ability to activate the dormant state of stem cells in the human body and have a repair effect on the damaged tissue and organ caused by the peroxidation and metabolic waste. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body’s ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Stem cells can also intervene the free radical stress to restore its normal function.
- Secrete nutritional factors: Stem cells can promote the tissue proliferation and differentiation within the damaged tissue and restore the physiological functions of tissues and organs.
- Regulate the immune function: Through the secretion of soluble factors and direct contact to regulate immune cells’ proliferation and its activity, stem cells are able to reduce the inflammatory response.
- Regulate the metabolic function: Using the ability of multi-directional differentiation, stem cells can enhance the efficiency of metabolic system, and thus accelerate the body’s operation and excretion of metabolic waste to promote the absorption of nutrients, so that maintain the normal physiological function.
In addition, studies have indicated that the paracrine effect is amplified because the donor cells are attracted to the damaged tissues that need their help. The damaged patient cells are secreting cytokines, regulatory proteins that act as mediators to generate an immune response that attract the donor cells. In turn, the donor cells secrete their own cocktail of proteins that stimulate the patient’s stem cells and help to reduce inflammation, promote cell proliferation, and increase vascularization and blood flow into the areas that need to heal. Paracrine effect cells can also secrete factors that inhibit the death of patient cells due to injury or disease.
An important third paracrine effect is their ability to ‘dampen’ the immune response that occurs during transplant rejection or during autoimmune disease. In this case the cells can be used directly or in conjunction with other stem cells for therapeutic purposes. For example, the application of mesenchymal cells along with blood stem cells during a bone marrow transplant seems to reduce graft versus host disease.
An advantage of using cells, versus medication, to promote regeneration is that transplanted cells will respond to their environment and secrete the factors as they are needed and in the appropriate concentration. The cells can be thought of as ‘drug factories’ that adapt as the tissue is repaired. Preclinical studies have demonstrated the efficacy of mesenchymal cells and cord blood cells for the treatment of neural, heart, kidney and muscle based diseases. There have been some convincing studies on the neuroprotective effect of cord blood cells.
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