A newly published medical article by researchers in Israel describes the case of a boy who developed tumors in his brain and spine four years after receiving fetal stem cell therapy for a rare genetic disease.
The case is reported by Ninette Amariglio and Gideon Rechavi from the Sheba Medical Center, Tel Aviv, and colleagues in the February 17 issue of the open-access general medical journal PLoS Medicine.
Most of the cells of the human body are highly differentiated, for instance the brain and spinal cord have two different types of cell: neurons that send electrical signals and glial cells that support and protect them. If these highly specialized cells become damaged or diseased, they can’t be replaced.
Scientists believe that neural stem cells (undifferentiated “master” cells that have the potential to become either of the two types of brain cell) could be the answer to making new brain cells to replace those damaged by stroke, trauma and degenerative diseases like Parkinson’s.
Critics of stem cell therapy, and of embryonic stem cell therapy in particular say it is not only ethically questionable but unsafe because of the risk of cancer (the stem cells multiply in much the same way as tumor cells) and also because the viruses used in some therapies can develop unpredictably in the recipient’s body.
In this case the boy, who is now 17 years old, was treated with human fetal stem cell therapy in 2001 at an unrelated clinic in Moscow, and four years later, scans revealed he had abnormal growths on his brain and spial cord.
The benign tumors are a rare side effect of fetal stem cell therapy, said the authors, who do not suggest research into therapies that use embryonic stem cells should cease but rather that their underlying biology and particularly their safety should be further investigated.
The authors said that the boy’s underlying condition, a rare genetic disease called Ataxia Telangiectasia that affects areas of the brain that control speech and movement and is caused by a mutation in the ATM gene, may have allowed the tumors to become established since the condition is often accompanied by a weakened immune system.
While this is the first documented case of a human developing tumors after receiving neural fetal stem cell therapy, there have been reports of rodents developing tumors after being injected with pluripotential embryonic stem cells. However, the risk of such tumors is thought to be much lower if the cells are differentiated beforehand.
The boy underwent stem cell therapy at a Moscow clinic, starting in 2001 when he received several injections of fetal neural stem cells into his brain and surrounding fluid. But after having an MRI scan at the Sheba Medical Center in Israel in 2005 because of recurrent headaches, the boy was found to have abnormal growths in his brain and spinal cord.
Surgeons removed the growth on the boy’s spinal cord in September 2006, when he was 14 years old. The growth on the spine has not reappeared but the mass in the brain has continued to grow slowly.
The growth removed from the boy’s spinal cord resembled a type of benign tumor called a glioneuronal tumor, and analysis showed it could not have arisen from the patient’s own tissue. The analysis showed for instance that the tumor contained both female (XX) and male (XY) cells and two normal copies of the ATM gene (whereas the boy’s own tissue would have had at least one mutated copy). The analysis also showed that the tumor contained cells from at least two donors.
The authors concluded that the findings:
“Do not imply that the research in stem cell therapeutics should be abandoned. They do, however, suggest that extensive research into the biology of stem cells and in-depth preclinical studies, especially of safety, should be pursued in order to maximize the potential benefits of regenerative medicine while minimizing the risks.”
“Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient..
Ninette Amariglio, Abraham Hirshberg, Bernd W. Scheithauer, Yoram Cohen, Ron Loewenthal, Luba Trakhtenbrot, Nurit Paz, Maya Koren- Michowitz, Dalia Waldman, Leonor Leider-Trejo, Amos Toren, Shlomi Constantini, Gideon Rechavi.
PLoS Med Vol. 6, No. 2, e1000029, published online 17 February 2009.
Sources: Public Library of Science.
Written by: Catharine Paddock, PhD