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  • STEM CELLS OVERVIEW

    Stem cells have attracted tremendous interest over the last few years as they have started to play a major role in the treatment and prevention of a number of degenerative diseases.  Below, you will find a brief introduction to stem cells and what makes them so unique in the treatment and prevention of degenerative diseases.

    What are Stem Cells?

    Stem cells are defined as cells with the unique capability to self-replicate throughout the entire life of an organism and to differentiate into cells of various tissues. The three specific characteristics to a stem cell include:

    • Self renewal
    • Remaining in the undifferentiated state
    • Differentiation potential to be a specialized cell

    Most cells of the body are specialized and play a well-defined role in the body.  For example, brain cells send and respond to electrical signals from other brain cells, liver cells produce biochemicals necessary for digestion, and pancreatic ß-cells produce insulin.  These cells have become specialized cells and will never differentiate into other types of cells or even proliferate.  By contrast, stem cells are primitive cells that remain undifferentiated until they receive a signal prompting them to become various types of specialized cell.  In an adult, they are stored and release by the bone marrow and serve as a repair system by being able to divide without limit to replenish other cells.  Upon receiving a specific signal, they divide and become another cell type with new specific functions, such as blood cells, brain cells, etc.

    Plasticity of Stem Cells

    Plasticity refers to the ability of a stem cell to differentiate into other cells.  The more plasticity a cell has, the more it can give rise to any type of human cells.  There are 4 main types of stem cell that occur at different stage of human development:

    • TOTIPOTENT STEM CELL is produced from the fusion of an egg and sperm cell and has the potential to give rise to any and all human cells.
    • PLURIPOTENT STEM CELL is the descendant of totipotent cell and is capable of giving rise to virtually any tissue type (begin after day 4 of embryonic division).
    • MULTIPOTENT STEM CELL is less plastic and a more differentiated stem cell.  It gives rise to a limited range of cells within a tissue type.  It can become one of several types of cells within a given organ.
    • UNIPOTENT STEM CELL only represents one cell type, its own, yet maintains the property of self-renewal which distinguishes it from non-stem cells.

    Classification of Stem Cells

    Several varieties of stem cell have been isolated and identified.  Very broadly, they comprise of two major classes:

    • Embryonic/fetal stem cells
    • Adult stem cells

    Embryonic stem cells (ESC) are cells extracted from the blastula, the very early embryo, while adult stem cells (ASC) are stem cells found in the body after birth.  The term “adult stem cells” does not refer to a characteristic associated with adulthood, but rather a contrast with the developing embryo.  Stem cells in the bone marrow of a new born baby, for example, or even stem cells found in the umbilical cord are referred to as adult stem cells.

    Embryonic/Fetal Stem Cells (ESC)

    Embryonic stem cells are derived from the inner cell mass of the blastula, the very early embryo.  ECS are pluripotent, and very short lived as they only exist in the early embryo.  As ESC develop and commit themselves to becoming the various cell types of the developing fetus, they gradually lose their pluripotency.

    To obtain these embryos, one must use a fertilized egg from which a whole human being can develop.  Many people understandably oppose the idea of using embryos; whom they already consider a legal person, for the purpose of extracting ESC.  Aside from these ethical and moral considerations, the use of embryonic stem cells is also still far from being clinically viable.  Many studies have shown that although at times ESC can give remarkable results, there is an amplificatory effect with ESC that may significantly increase the risk of developing tumors.  At Thai Regen, we do not use Embryonic stem cells.

    Adult Stem Cells (ASC)

    Similar to ESC, it has been found that ASC can self-renew and differentiate into specialized cells of various tissues.  ASC are continuously generated in small quantity by the bone marrow and can be found in tissues around the body.  The role of ASC is to maintain and repair the tissue in which they are found, but seem to be involved only in relatively minor repair of the tissue in which they reside.  In case of major injury or degeneration, the need for stem cells far exceeds the number of stem cells available in the tissue, and stem cells from the bone marrow (BMSC) are called to contribute to the repair process.

    Although ASC are most predominantly found in the bone marrow, studies have shown that they can also be isolated from various tissues such as liver, intestine, muscles, brain, pancreas, baby teeth, blood as well as taken from the placenta.  Currently, the major sources of ASC for stem cell therapy include:

    • Bone marrow
    • Peripheral Blood Stem Cells (PBSCs)
    • Placenta/Umbilical cord blood stem cells


    Bone Marrow Stem Cells (BMSC)

    Bone marrow is the spongy tissue in the center of bones.  Its main function is to make blood cells that circulate in your body and immune cells that fight infection.  Bone marrow was the first source used for stem cell transplants; bone marrow transplantation for the treatment of blood cancer (leukemia) started 40 years ago, because it has a rich supply of stem cells.  The bones of the hip contain the most marrow and thus have large numbers of stem cells.  For this reason, cells from the hip bone are used most often for a bone marrow transplant.  Enough marrow must be removed to collect a large number of healthy stem cells.

    For a bone marrow transplant, the donor gets general anesthesia (is put into a deep sleep).  Several large needle punctures are made through the skin into the back of his or her hip bone to remove marrow.  The marrow is pulled out through the needle into a large syringe.  Aside from the risks of general anesthesia, the main side effect is that the donor is sore for a few days afterwards.

    Peripheral Blood Stem Cells (PBSC) – also known as Hematopoietic Stem Cells (HSC)

    Normally, very few stem cells are found in the blood.  However, by giving hormone-like substances called stem cell mobilization growth factors to stem cell donors, this issue can be overcome.  Basically, the stem cells mobilization growth factors given to the patient will cause the bone marrow to generate a large quantity of stem cells that will migrate over a few days from the bone marrow into the circulating blood.  The stem cells will then be removed or harvested from the circulating blood through a process called apheresis (from the Greek “aphairesis” for removal).  This simple procedure takes a few hours.  A catheter (a very thin flexible tube) is put into a vein in the donor’s arm and attached to tubing connected to a special machine.  The donor’s blood is run through this machine which separates and keeps only the red blood cells that contain the stem cells.  The rest of the blood is returned to the donor. 

    Placenta and Umbilical Cord Blood Stem Cells (Cord Blood Stem Cells)

    A certain amount of stem cells are normally present in the blood of newborn babies.  After birth, the blood that is left behind in the placenta and umbilical cord (known as cord blood) can be collected and stored for later use in a stem cell transplant. After the umbilical cord is clamped and cut, the placenta and umbilical cord are cleaned and cord blood is collected in a sterile container.  The cord blood is mixed with a preservative solution and frozen until needed.  Cord blood transplant uses blood that would otherwise be discarded.  It is fairly easy to collect and does not pose a risk to the donor.

    Types of Stem Cell Transplantation

    • A stem cell collected from the same patient on whom they will be used is referred to as autologous
    • A stem cell collected from another donor is referred to as allogeneic
    • A stem cell collected from identical individuals is referred to as syngeneic


    Autologous Stem Cell Transplant

    In this type of transplant, you are your own donor, using stem cells from either your bone marrow or circulating blood.  Your stem cells are removed or harvested before treatment, sent to a laboratory for analysis and activation and injected back to your body.  An advantage of autologous stem cell transplant is that you are getting your own stem cells back.  This means there is no risk that your immune system will reject the transplant or that the transplanted stem cells will attack your own body.

    Allogeneic Stem Cell Transplant

    Stem cells do not come from the patient, but from a donor whose tissue type best matches the patient. The donor is most often a family member, usually a brother or sister.  If you do not have a good match in the family, a donor may be found from the general public through a national registry.

    There are some possible drawbacks to allogeneic stem cell transplant.  The transplant, also known as a graft, may not “take” — that is, the donor stem cells may be more likely to die or be destroyed by the patient’s immune system before settling in the bone marrow.  Another possibility is that the donor stem cells will make new immune cells that attack the recipient’s body — a condition known as graft-versus-host disease.  There is also a very small risk of certain infections from the donor stem cells, although donor stem cells are always tested beforehand to minimize this risk.

    Syngeneic Stem Cell Transplant

    This is a special kind of allogeneic transplant because the donor is an identical twin with identical tissue type.  Since few people are identical twins, this type of transplant is very rare.  An advantage of syngeneic stem cell transplant is that graft-versus-host disease will not be an issue.

    Which Stem Cell Source Is Best?

    All 3 sources of stem cells can be used for the same goal: to give the patient healthy stem cells to either assist with the rejuvenation and prevention of a degenerative disease or assist in repairing damaged organs and tissues as needed.

    Historically, all stem cell transplants were done by marrow transplants.  Today, peripheral blood stem cell transplantation (PBSC’s) is by far the most common and practical way to treat a patient.  Often, doctors are able to harvest more stem cells from peripheral blood than from bone marrow.  The donation procedure for peripheral blood stem cells is also easier on the donor than donating bone marrow.  Another plus for peripheral blood stem cell transplant is that the recipient’s blood count often recovers faster than with a bone marrow transplant.

    Cord blood transplant from the placenta and umbilical cord of newborns is usually considered an alternative source for stem cell therapy if a good match can be found at the stem cell bank.  But it is still a new technique and the number of stem cells available from the donor source is often too low for large adults, so this source of stem cells is used mostly in small adults and children or in combination with another stem cell source.  Cord blood stem cells also usually take longer to engraft, leaving the patient at a higher risk of infection compared to transplanted marrow or peripheral blood stem cells.  Another drawback is that unlike bone marrow transplant or peripheral blood stem cell transplant, once the donated stem cells from the cord blood are used, the donor cannot be called back to give more if needed.

    How Do Stem Cells Repair the Body – Stem Cells Homing and Engraftment

    What has emerged over the past few years, through a vast body of scientific literature, is the novel view that the process of repair and rejuvenation taking place in the body involves adult stem cells.  Although it is not yet absolutely clear on how the bone marrow adult stem cells participate in the body healing process, many scientific studies support the following theory.

    When a tissue is subjected to significant stress, stem cells originating from the bone marrow migrate to that tissue, proliferate, and differentiate into cells of that tissue, thereby supporting the repair process.  This can happen because the damaged tissue releases a messenger called G-CSF (Granulocyte colony-stimulating messenger) that triggers stem release from the bone marrow, increasing the number of stem cells circulating in the blood.  In addition, the damaged tissue also releases another unique messenger called SDF-1 (Stronomal-Derived Factor 1) known to attract stem cells.  SDF-1 factors bind to stem cell receptors and assist in the migration of stem cells to the damaged tissue where stem cells proliferate and then differentiate into cells of that tissue to assist in the repair.  This process by which stem cells are attracted and migrate into a damaged tissue, as opposed to a healthy tissue, and differentiate into the desired cell types to assist in repairing the damaged tissue is called homing.  This process if fairly rapid and has been measured in hours and no longer than 1 or 2 days.

    After the successful homing of stem cells into the damaged tissue, the next step to occur is called engraftment.  In this process, the new stem cells anchor themselves and fuse with the host cells to create a new healthy engrafted tissue.  This seems to occur by the apparent reprogramming of gene expression in the resulting hybrid cell.  For the engraftment to be successful, the stem cells must survive in the recipient, integrate in the surrounding tissues, and function appropriately for the duration of the recipient’s life.  It has been shown that short-term engraftment can range from weeks to a few months while durable long-term multilineage engraftment have been shown to take many months in mice and years in patients.

    Limits of Stem Cells

    Since in theory the body has its own repair system and the capability to regenerate itself then why does the body age?  Why do people become terminally ill?

    Several theories have been put forward to try to answer these questions.  One popular theory is that even though special messengers are released by damaged tissue to attract stem cells, they often do not migrate in sufficient quantity, or may even fail to arrive at all because of blocked blood vessels.  The healing process of the damaged tissue therefore may occur very slowly, if at all.  If the body is sufficiently weakened, the disease may also spread from there on to other parts of the body.  Another possibility is that some of the diseases that develop are not recognized as such and no messengers are sent out to call for repair.  Another major factor seems to be that with age, the generation of adult stem cells diminishes reducing the ability of the body to repair itself.

    Stem Cell Therapy Delivery System

    A stem cell based therapy will depend heavily on the proper delivery of stem cells to the damaged area.  For a successful stem cell based therapy to work, it is believe that the following series of events have to occur once the patient is injected with the stem cells:

    • Proliferate extensively and generate sufficient quantities of tissues
    • Differentiate into the desired cell types
    • Survive in the recipient
    • Integrate in the surrounding tissues
    • Function appropriately for the duration of recipient’s life

    Although the process of aging cannot be stopped, recent developments have shown that by extracting stem cells from the body, cleaning them, concentrating them, and injecting them back into the body for the natural process of homing and engraftment to occur, in many cases, the body’s own healing process can be enhanced and quality of life improved.