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Stanford Researchers Announce Immune Problems With Embryonic Stem Cells

Scientific American, August 22, 2008

Following experiments with mice, Stanford University scientists have announced that stem cell therapies which use human embryonic stem cells (hESCs) have a high probability of failing because of immune rejection. In these studies, mice that were injected with hESCs exhibited an immune response which is at least as severe as that triggered by organ transplantation. Consequently, all the transplanted stem cells were killed by the immune system within a week. The Stanford researchers used molecular imaging technology to monitor the hESCs after injection, which revealed that the hESCs began dying within a week of injection and were completely dead by 10 days. When more hESCs were subsequently injected, they were found to die much more quickly, within 2 to 4 days, due to the already fully activated level of the immune system defense response. Even when the animals were given tacrolimus and sirolimus, two mediations that are commonly used to suppress an immune response, the hESCs lasted 28 days before dying but were still rejected and killed by the immune system. Additionally, in all cases, the overall health of the animals continued to deteriorate, and the researchers were not able to determine any benefit from an increase in time before all the hESCs were eventually destroyed.

The U.S. FDA (Food and Drug Administration) has not approved the use of hESCs as a medical therapy, primarily because of the danger of teratomas, which are a well established risk of hESCs. A teratoma is a specific type of tumor which contains cells from all 3 germ layers of the body, which have often differentiated into specialized tissue such as teeth, hair and organs, and which therefore make these tumors particularly hideous and dangerous. The ability of embryonic stem cells to form teratomas is, in fact, the defining trait of embryonic stem cells, and the ability of a cell to form a teratoma remains the universal laboratory test by which embryonic stem cells are identified: namely, if an unknown cell is found to form a teratoma in the laboratory, then it's an embryonic stem cell, whereas if it doesn't form a teratoma, then it's not an embryonic stem cell. Teratoma formation, however, is certainly not the only risk posed by embryonic stem cells, and once again we are now reminded of the dangers of immune rejection that are inherent in embryonic stem cells. Adult stem cells, by sharp contrast, do not pose any risk of teratoma formation, and some types of adult stem cells, such as mesenchymal stem cells (MSCs), are known to be "immune privileged", meaning that they do not trigger an immune response.

According to Dr. Joseph Wu, a Stanford radiologist who led the recent research, these findings, which reveal such a strong immune rejection of embryonic stem cells, constitute "a reality check".



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