John Bovill Cell Based Therapy

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Stem Cell Based Therapy

  • Stem cells have been used for many years with more and more therapies being developed experimentally and theoretically. Such therapies being used today include, but are not limited to: bone marrow transplant, blood stem cells, umbilical cord blood stem cells, engineering skin tissue, and experimental organ treatments.

Blood and Bone Marrow Transplants

Background on Bone Marrow

http://www.wisegeek.com/what-is-a-bone-marrow-stem-cell.htm#didyouknowout
  • Bones are made up of bone marrow, which contributes to overall blood cell count in the body. The bone marrow is unlike the calcified hard exterior of bone, but rather is soft, spongy, and on the inside. (11) The bone marrow was identified as a source of potential cell treatment and transplant because it contains hematopoietic cells, that can turn into several other types of cells. Sound familiar? These cells can transform into any type of blood cell (white, red, or platelet), and/or into more bone marrow cells.
  • The transplantation of bone marrow has been a proven treatment for many decades. More recently, there has been a shift from collecting stem cells from the bone marrow to collecting stem cells from the blood. Because of this the procedure is called a stem cell transplant. In general terms, whether it is a blood or bone marrow transplant, the end goal is to replenish and replace abnormal blood-forming cells with functioning healthy blood-forming cells. (10)
    • These abnormal blood-forming cells are the general cause of many diseases and cancers, e.g leukemia, thus if this goal is successfully reached, the disease may be cured.

Importance of Transplant

https://courses.lumenlearning.com/ap1/chapter/cellular-differentiation/
  • As mentioned, there are certain diseases, leukemia, immune deficiency disorders, lymphomas, etc, that are detrimental to the body, because they keep the hematopoietic stem cells from developing normally. A defect or abnormality in the development of hematopoetic stem cells ultimately leads to blood cells being dysfunctional. (16)
  • If successful, a bone marrow transplant has the capability to replace stem cells that were damaged or demolished due to chemotherapy treatment for curing cancer in other tissues. It is the hope that the bone marrow can repopulate the entire blood system in the new host.

Types of Stem Cell Transplants

  • Autologous transplant (16)
    • Otherwise called high-dose chemotherapy with autologous stem cell rescue, you get your own stem cells after physicians treat your cancer.
  • Allogeneic transplantation (16)
    • You receive stem cells from another person, but it is not as simple as it sounds. Bone marrow is not consistent person to person, it is crucial that when participating in allogeneic transplantation that you find someone whose bone marrow complements yours.
      • The optimal donor should have as many human leukocyte antigens (HLA) like yours as possible. HLA proteins are found on your white blood cells, which aid in fighting infections. The challenge to finding the perfect match is just one of them many obstacles that arise in allogeneic transplantation.
    • In allogeneic transplantation, the amount of chemotherapy that a patient receives depends on his or her age, health and the specific disease being treated.
  • Umbilical cord blood transplant (16)
    • The next best option, if one cannot find a donor match, is to use cord blood. After the birth of a baby, the umbilical cord can be used as a source of stem cells that can be substituted for bone marrow stem cells. The blood cells from an umbilical cord are used with more confidence in transplantation because they have not developed cell-surface molecules that the host's immune system could recognize and attack, thus are immune rejected less often by the host.
  • Parent-child transplant and haplotype mismatched transplant (16)
    • A type of transplant more commonly used, yet the match is only 50% with the host, rather than 100% increasing chance of immune rejection. The cell donor is likely a parent, child, brother, or sister.

The Process of Transplantation

https://www.cancercompass.com/cancer-guide/conventional-treatment/stem-cell-transplant.html
  • For a successful transplantation, certain steps must be followed. (11) (16)
    1. Collecting your stem cells: Commonly patient's or host's white blood cell count is increased with injections of medication and the cells are collected from the blood through a transplant catheter and frozen until after the therapy.
    2. Transplant treatment: Patient receives high doses of chemotherapy, and sometimes radiation therapy. This is done in hopes of diminishing or destroying the disease, and lowers cell count of abnormal or dysfunctional cell count, which has its risks too.
    3. Getting your stem cells back: Patients receive a stem cell transfusion in which your physician puts your or your donor's stem cells back into your blood through the transplant catheter.
    4. Recovery: It is critical that the patients take antibiotics and other drugs, including medications to prevent graft-versus-host disease and further immune rejection. A patient may receive additional blood transfusions if necessary.

Experimental Outcome

  • Receiving a bone marrow transplant can be a very risky operation and is usually associated with infection, bleeding, and low blood oxygen due to low numbers of white blood cells that fight infections, platelets that help with the clotting of blood, and red blood cells that carry oxygen, respectively. (12) Clinically it has been shown that your blood counts can eventually return to safe/normal levels. The vast amount of chemotherapy lowers your blood count and reduces the blood cell functions, so a successful transplantation will renew your blood cell count to a healthy level.
    • Therefore, a successful transplantation is when your cancer or disease is no longer present or at least is in remission.

Organ Treatment/Transplant

  • Pluripotent or induced pluripotent stem cells as previously mentioned provide a potentially unlimited source of human cells that derive most of the cell types of the body. The ability to isolate and induce pluripotency has led to the desire to use stem cells to provide organ treatments or transplants of the heart, lung, liver, and kidney. This due to the minimal supply of functional and healthy donor organs and the inevitably long wait times. Through the use of stem cells, new organs could potentially be grown at will or used to repair damaged organs. (14)
  • The IPCs have the capability to differentiate into lung epithelial cells (lung), cardiomyocytes (heart), hepatocytes (liver), and renal epithelial cells (kidney). Similar to bone marrow treatment that aims to replenish healthy blood levels to cure diseases, the treatment of organ tissues using stem cells is important because it should revamp the respective organ to its original high functioning power and reduce the effect that the disease had on the body by diminishing the function of the organ in question. (15)

Exprimental Spinal Cord Injury Repair

http://www.medstartr.com/project/detail/772
  • Injury to one's spinal cord can have dramatic life changing effects and the ability to potentially repair such injuries would provide many individuals with increased quality of life. Results have shown that when human neural stem cells have been grafted into mice with injuries to their spinal cord, the cells differentiate correctly and are able to help the mice recover their general motor function. (14)

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