Wise Young


All cells have the potential to cause tumors. Some cells are more likely to produce cancer than others. A tumor is not necessarily a cancer and we should discuss that first. A tumor is a growth of cells that is an inappropriate amount or type of cells for the tissue. Thus, for example, a wart is a tumor. If a hair is growing int he spinal cord, that is a tumor. In contrast, a cancer is a cell that is growing out of control and that does not respond to most tissue factors, spreading across tissue boundaries and often into adjacent tissues and into blood of lymphatics to spread.

Embryonic stem cells do have a propensity to grow without regard to their surroundings. They are in fact the only stem cells that do not need other cells in order to produce all the cells of the body. That is why they must be differentiated before tranplantation. Otherwise, they cause tumors called teratomas which have many types of cells in them, including hair and skin.

Adult stem cells need other cells to interact with before they can produce cells that are tissue specific. The sites of these interactions are called niches. There has been much experience with transplantation of bone marrow stem cells. In order for bone marrow (or umbilical cord blood) cells to engraft, the cells occupying the niches must be removed. This is done chemo- or radiation therapy. Stem cells that settle into that niche then will make blood cells.

The niches for the central nervous system are not known. However, a great deal of attention has been focused on the subventricular zone (SVZ) where adult neural stem cells are known to reside. The SVZ sends out a stream of migrating neural stem cells to the olfactory bulb and the hippocampus, called the rostral migratory stream. The spinal cord is also believed to be a site of neural stem cells. However, we don't know which they are. For some time, the neural stem cells of the spinal cord were believed to be ependymal cells. However, several studies suggest that the stem cells may be more scattered in the spinal cord. We don't have any easy way of displacing stem cells from the neural niches that they occupy.

The study of Joanne Kurtzberg, showing beneficial effects of umbilical cord blood transfusion in children with Krabbés disease was very surprisng and encouraging. This is a deadly genetic disease where the brain has a mutated GalC gene, the brain demyelinates, and the kids usually end up severely retarded and dead after several years but early treatment with umbilical cord blood can save them and prevent further brain damage. The kids are not treated with any chemotherapy to open up the niches (Source). This raises the question whether it may be possible to transfused stem cells in situations where there is brain damage and “niches“ in the brain may be available for occupancy by cells that are just infused intravenously. This of course is the theory by which many clinical centers are not infusing cord blood or bone marrow cells intravenously for neurological disorders.

Umbilical cord blood transplants is likely to become the treatment of choice for babies with rare neuorlogical genetic diseases. These include, for example, the disease adrenoleuodystrophy (the disease described in Lorenzo's oil), Hurler's syndrome, metachromatic leukodystrophy, Tay-Sachs disease, Sandhoffs disease, and others (Source). Umbilical cord blood has been used for many years to treat hematopoietic disorders. I believe that the first case of a cord blood transplant was done in the early 1990's for somebody who had Fanconi's anemia and received a unit of umbilical cord blood from a relative. He apparently was cured. There was an enormous struggle during the 1980's to get doctors to take umbilical cord blood seriously.

I met a man recently at a New Jersey High Tech Hall of Fame induction by the name of Kenneth Moch (Source). He was the CEO of a company called Biocyte that pioneered umbilical cord blood cell transplants in the 1980's. The three scientists who founded the company were Gorden W. Douglas, Hal E. Broxmeyer, and Edward A. Boyce and they received patent 5,004,681 for their work (Source) Kenneth Moch reminded me that the word stem cell was really accepted by most doctors and cord blood was thought to be a scam in the 1980's. It took over 20 years for the field to reach respectability. It is still a struggle. Many fly-by-night clinics are trying cord blood cells on various diseases without doing rigorous trials to demonstrate efficacy.

Probably over 10,000 people get bone marrow or cord blood cell transplants per year in the United States. While the mortality rate of such transplants is high, on the order of 5-10%, this is due to the nature of the disease for which the transplants are being done (leukemia, genetic anemia, autoimmune diseases) and the requirement of bone marrow ablation. Over 190,000 cord blood units are available for transplantation around the world (Source). The incidence of cancer associated with cord blood transplants is very low. It is actually quite hard to find the data because cord blood is frequently used to treat people with cancer. Cases where the cord blood actually caused the cancer is difficult and, to my knowledge, not reported. There are a major clinical trials studying this right now and I hope that the data will be available:
http://clinicaltrials.gov/ct/show/NCT00008164?order=1

In 2004, Laughlin, et al. published a very influential paper in the New England Journal of Medicine (Source). They found essentially that there was no differences in the outcomes after cord-blood transplantation and bone marrow transplants. They conclude that “HLA-mismatched cord blood should be considered an acceptable source of hematopoeitic adults in the absence of an HLA-matched adult donor“. While this might not sound very impressive, it is important to point out that this study is not a controlled study and there were major differences between the patient populations studied. First, cord blood recipients tended to be younger and more likely to have advnaced leukemia than bone marrow recipients. Second, they received lower doses of of nucleated cells and their hematopoietic recovery tended to be slower. Third, acute graft-versus-host disease (GVHD) was significantly greater in the bone marrow recipients. What the study did not compare were matched cord blood and matched bone marrow transplants. The reason is of course because matched bone marrow transplants (6/6 HLA antigens) are still considered the gold standard of the field and cord blood is used only when matched marrow iare not available (Source).

Can bone marrow cells produce tumors? If the cells are unmanipulated, they are very unlikely to produce tumors after transplantation. Allografts (from another person) can cause GVHD (Graft versus Host disease) but this does not occur with autografts (from oneself). So, the risk of an autograft producing cancer or GVHD is low. However, you ask about the manipulation that the cells are undergoing and the FDA status of the cells. If the cells are manipulated either by growth factors or genetic modification, the US FDA requires safety tests for cancer and other problems before they will allow the treatment into clinical trial. European FDA's likely to require these as well.

Wise.




Quote:
Originally Posted by ttma
hi,

i have done some searching about that, i would like others to share with me these links:

articles about new studies about the posibility of adult stem cells to cause cancer:

http://news.bbc.co.uk/1/hi/health/4465717.stm

http://www.newscientist.com/channel/...therapies.html

http://www.newscientist.com/article....mg18624965.200

i was discussing these links with one of the representitives of a stem cell company, and he was saying that tumors could occur only if the stem cells were divided out of the body, but in his company ( xcell ) they don't do that actully, all they do is getting the cells from bone marrow, isolating them, then reinjecting.

i am seriously thinking about having the therapy, but still worried about the cancer thing, and what i need to take the decision is more information..

any one who can help please do so..

thank you
http://sci.rutgers.edu/forum/showthr...504#post641504