Fetal Stem Cell Therapy Could Prove Fatal

An Israeli boy who suffers from a rare, often fatal genetic disease known as ataxia telangiectasia (A-T) has developed a tumor that was directly traced to the fetal stem cell therapy that he received. No known cure exists for A-T, which causes degeneration of the brain regions that control movement and speech, and people with the disease usually do not survive past their teens or twenties. Consequently, when the boy was 9 years old, his family traveled to Moscow so that he could receive an experimental therapy consisting of intracerebellar and intrathecal injections of human neural fetal stem cells – derived from aborted human fetuses – which were then injected into the boy’s brain and spinal cord as a treatment for his A-T. Even though he received two more treatments with the fetal stem cells at the ages of 10 and 12, he still had not shown any improvement by the age of 13 and in fact the severity of his disease had progressed to such an extent that he required a wheelchair. When he began having headaches, tests conducted at the Sheba Medical Center in Tel Aviv revealed a multifocal brain tumor pressing against both his brain stem and his spinal cord, which biopsy revealed to be a glioneural neoplasm. The tumor was surgically removed in 2006 when the boy was 14 years old, at which time cytogenetic and molecular analysis of the tumor revealed it to be of the same tissue as the fetal stem cells, and was therefore caused directly by the fetal stem cell therapy. Among other tests, genetic analysis revealed that some of the cells of the tumor had originated from a female donor and were comprised of 2 normal, healthy copies of the gene in which mutations cause the A-T disease, and which therefore did not match the boy’s own genotype containing abnormal copies of the gene.

Had this tumor not been discovered and surgically removed, it certainly would have been fatal and the boy would have died – not from the A-T disease, but from the therapy which was meant to treat the A-T disease. Indeed, one of the most serious concerns with embryonic and fetal stem cells is that they might constitute “therapies” which are worse than the diseases that they are meant to treat. This particular example with a boy suffering from A-T offers strong evidence to justify exactly such a concern. The boy is being closely monitored for any other tumors which might also possibly develop over time, as a lingering yet direct result of the fetal stem cell therapy that he received.

The formation of tumors has long been one of the main concerns associated with embryonic and fetal stem cells, and the fact that this boy’s tumor was not detected until 4 years after his first treatment raises some new concerns. According to Dr. Marius Wernig of Stanford University, “Stem cell transplantations have a humongous potential. But if people rush out there without really knowing what they’re doing, that really backfires and can bring this whole field to a halt.”

As Josephine Quintavale of the public interest group Comment on Reproductive Ethics adds, “The risks of tumor formation in association with embryonic stem cells are widely acknowledged and one reason why there are very serious concerns about the proposed use of such cells in treating spinal cord injury in the US. It would appear from this report that fetal stem cells are similarly unstable. These are not areas of therapy we should be rushing into, whatever the ethical debates surrounding the use of embryo or fetal tissue per se.”

Dr. Stephen Minger of King’s College London further explains, “This is worrying and we have to be cautious. We need to have long term monitoring and follow-up of the patients who are given stem cells and rigorous regulation of centres providing cell therapy. Although this is just one case, it does show that we need to be careful about the cell population we are using.”

As we have often explained on this website, all stem cells are not created equal, nor do they behave equally, and important distinctions must be made between the different types of stem cells. Generally speaking, all stem cells fall into 2 broad categories: adult stem cells, and everything else. The latter category includes embryonic and fetal stem cells, while stem cells that are derived from umbilical cord and placental blood are categorized as “adult” stem cells. The relatively recently discovered endometrial regenerative cells (ERCs), which have shown to be particularly promising, also fall into the category of “adult” stem cells. It is important to understand that adult stem cells behave very differently from embryonic and fetal stem cells, with one of the major differences being the risk of tumor formation, which has long been known to be inherently problematic in embryonic and fetal stem cells, especially in regard to the formation of teratomas (a specific type of tumor), which is the definitive requirement of pluripotency; by sharp contrast, however, adult stem cells do not cause tumors because adult stem cells are not pluripotent, but are instead multipotent, at best. In the past, the lack of pluripotency in adult stem cells was seen as a disadvantage, although increasingly it is being recognized as a distinct advantage, since it eliminates any danger of tumor formation.

According to a warning issued by Dr. John Gearhart, a stem cell scientist at the University of Pennsylvania, “Patients, please beware. Cells are not drugs. They can misbehave in so many different ways, it just is going to take a good deal of time.”

Although this particular case of tumor formation was originally reported in the PLoS medical journal, a peer-reviewed open access journal published by the Public Library of Science, the story was subsequently republished in all major media outlets around the world. As the authors of the PLoS paper cautiously conclude, “This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.”

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