Trial leader Masayo Takahashi speaking about the medical applications of iPS cells in November last year (Image: Nippon News/Alamy)

A pioneering stem-cell trial has been halted after genetic mutations were discovered in the cells of the second trial participant. One of the mutations may carry a remote risk of cancer.

The trial is the first to explore whether a type of stem cell known as induced pluripotent stem (iPS) cells can be used to treat disease. These are made by taking cells from a patient’s skin and “rewinding” them to a premature stem-cell state using a cocktail of growth factors. The cells can then be converted into the type of cell required, before being transplanted back into the patient.


In this case, patients’ skin cells were turned into specialised retinal cells in an attempt to reverse the damage caused by age-related macular degeneration, a common form of blindness in older people. The first patient, a 70-year-old woman, was treated last September, and is reportedly in good health.

There is a lot resting on the outcome of the trial. It could provide the first glimpse of the clinical potential of iPS cells, which were created for the first time in 2006.

Where did they come from?

“It’s true that a mutation was found in the cells before transplantation into the second patient, and this is something we took into account when we made the decision to suspend the study for the time being,” says trial leader Masayo Takahashi of the Riken Center for Developmental Biology in Kobe, Japan.

Analysis of the patient’s cells revealed six mutations. Three were genes that had been deleted and three were changes to nucleotides, including one in an “oncogene” linked with a low risk of cancer. The mutations were not detectable in the original skin cells from the patient, suggesting that they probably occurred as a result of the iPS-cell procedure. “Either they were there at undetectable levels in the skin cells, or they were caused by the iPS cell induction process,” says Shinya Yamanaka of Kyoto University in Japan, one of the scientists who developed the reprogramming technique. “However the risk of carcinogenesis was considered low.”

In addition to the discovery of the mutations, a second reason for the pausing of the trial is that regulatory changes in Japan mean that now only certain types of institution can run stem-cell trials, Takahashi told New Scientist. Once the team members have worked out how to accommodate these changes, they hope to resume the trial and test a further five patients using healthy, mutation-free skin cells from younger donors.

“I think it’s an easily fixable problem if they go this route,” says Robert Lanza, chief scientist at Ocata Therapeutics (formerly Advanced Cell Technology) in Marlborough, Massachusetts, a company that is also developing stem-cell therapies for age-related blindness.

Worrying discovery

Nonetheless, the discovery of mutations that are likely to be related to the iPS-cell process is a disconcerting finding, and one that stem-cell scientists have been worried about since the field’s infancy. One of the benefits of stem-cell therapies is that the cells can multiply rapidly – but this is also a characteristic shared by cancer cells.

However, other scientists urged caution. “It’s important to understand that even mutations in oncogenes don’t guarantee that cancer will result,” says Jeanne Loring of the Scripps Research Institute in La Jolla, California.

“It will be important to determine the source of the mutation before jumping to conclusions that reprogramming cells will always carry this sort of risk,” says Mike Cheetham of the Institute of Ophthalmology at University College London.