Stem cell therapy triggers tumor

A neural stem cell transplant from fetal cells performed in Russia led to a brain tumor in a teenage boy, researchers in this week's PLoS Medicine report, raising concerns about the safety of neural stem cells treatments.

MRI of brain lesion, courtesy of PLoS Medicine

The researchers confirmed that the cancer originated from the donor tissue, not the boy's own cells. This is the first report of cancer following fetal neural stem cell transplant. However, outside experts raised concerns about the safety of the transplant procedure used in this case, suggesting that other stem cell transplants conducted with more oversight may not carry an increased risk. The boy suffered from a recessive genetic disorder called ataxia telangiectasia (AT), an incurable, neurodegenerative disease that has left him wheelchair-bound. In 2002, when he was 9, his parents took him from Israel to Moscow to undergo experimental stem cell therapy. A team of researchers in Moscow injected multiple transplants of neural stem cells, which were derived and purified from the brains of aborted fetuses. Four years later, the boy was diagnosed with a very slow growing form of cancer called glioneural neoplasm after coming to the Sheba Medical Center outside Tel Aviv, Israel, complaining of headaches. A team led by Gideon Rechavi, a pediatric hematologist and oncologist at Sheba Medical Center, performed a histological analysis on the tumor to determine its makeup. They found it contained a hodgepodge of different cell types -- this is unlike most brain tumors, which arise from a single cell type, he said. The different types suggest that the tumor "originated from a stem cell that can differentiate towards various directions," said Rechavi. To rule out the possibility the tumor came from the boy's own cells, given that AT weakens the immune system and can predispose patients to cancer, the researchers tried to determine its source. The team found that the tumor could not have arisen from the boy, because he is homozygous for the mutation that causes AT, while the DNA from the tumor cells carried only the normal allele. "This paper does a very good job of showing that the cells that constituted this tumor did not arise from the patient and [were] not genetically identical to either of the parents, and clearly came from the donor tissue," said Arnold Kriegstein, a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, San Francisco. The case study raises a number of questions. Because the patient's immune system was impaired, it's not yet clear whether the increased risk of cancer is specific to patients with suppressed immune systems, something particular to the procedure done in Moscow, or a danger with neural stem cell transplantation in general, said Uri Tabori, a pediatric hematologist and oncologist at the Hospital for Sick Children in Toronto, Canada. "This is a case report," he said. "It has its role in saying it can happen, but we don't know if it's common, if it's uncommon," he said. "It's a cautionary tale for studies currently being done in the US and elsewhere," said Kriegstein. Since the patient developed the brain tumor four years after the initial injections, researchers may need to monitor patients for a long time after a treatment to evaluate safety, Kriegstein said. However, it's premature to translate these findings to studies conducted in the US, said Aileen Anderson, a neuroscientist who studies stem cells at the University of California, Irvine. The researchers who conducted the transplant followed the protocol of a group that has published only one other paper in an international, peer-reviewed journal, and the cells used are a mixture of glial cells, neurons, and progenitors -- "a sort of cell mush," she said. These are "completely uncharacterized populations, populations that would never be accepted in the US or any first-world country," she said. Kriegstein agreed. "It's absolutely scary," that the group conducted the transplant, he said. Currently, a company called Stem Cells, Inc., is conducting a Phase I clinical trial to evaluate the safety of fetal neural stem cell transplants for treatment of Batten Disease, an invariably fatal neurodegenerative disorder that affects young children.
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[14th January 2008]*linkurl:Single-factor stem cells;http://www.the-scientist.com/blog/display/55399/
[5th February 2009]*linkurl:The ecology of tumors;http://www.the-scientist.com/article/display/23276/
[1st April 2006]