BioEd Online

A report claiming that unregulated transplants of human fetal neural stem cells led to tumours in a boy's brain and spinal cord is being hotly discussed by stem-cell researchers. Although the procedure took place well outside the scientific mainstream, it underscores the need for caution as clinical trials involving stem-cell transplantation move forward.

"This is the first documented case of tumours resulting from fetal-cell transplant," says Wise Young, a neurosurgeon at Rutgers University in Piscataway, New Jersey.

The paper, appearing in PLoS Medicine, describes a boy who received injections of fetal neural stem cells — for the neurodegenerative disease ataxia telangiectasia — at a Moscow clinic at the ages of 9, 10 and 12 (N. Amariglio et al. PLoS Med. 6, e1000029; 2009). When he was 13, researchers from the unrelated Sheba Medical Center in Tel Aviv, Israel, identified growths in his brain and spinal cord. The following year, spinal tumours were surgically removed. Within the growths, the team found cells that could not have arisen from the patient and must have come from at least two fetuses.

Gideon Rechavi, the team leader, says he has communicated with the Moscow clinic only through the boy's parents. He declines to disclose its identity, but says those involved apparently did not characterize the cells well. Rechavi adds that the boy's disease, which affects the immune system, may have made it easier for the tumour to grow.

During the past three months, three biotech companies have received regulatory authority to proceed with clinical trials that transplant fetal stem cells into the brain or cells derived from embryonic stem cells into the spinal cord. All three — ReNeuron of Guildford, UK; Geron of Menlo Park, California; and StemCells of Palo Alto, California — have presented preclinical data on safety and efficacy for their cells.

John Sinden, ReNeuron's scientific co-founder, says that "there are almost no similarities" between the Moscow procedure and his company's clinical trial. He argues that one isolated case doesn't threaten the whole field.

It might, though, serve as a cautionary tale, says Steven Goldman, chair of neurology at the University of Rochester in New York and an adviser to the US Food and Drug Administration. He believes that many techniques that induce stem cells to expand in culture render them more likely to grow inappropriately. "I hope it makes people think twice about how cells are isolated and maintained before transplant," he says.

"This paper is actually a really good thing for the field," says Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland, Ohio, who has led efforts to help patients assess the risks of stem-cell procedures. "People who undergo these cell-based therapies have a responsibility to share any adverse events that happen," he adds.

However, Theo Palmer, a neurosurgeon at Stanford University School of Medicine in California, says the new report is unlikely to do much to help researchers understand or avoid risk. The Moscow cells may or may not have qualified under the strict regulations for human stem-cell trials. "This makes it impossible to draw parallels to other neural-stem-cell studies performed under rigid safety criteria," he says.