A PIONEERING stem-cell trial has been halted after genetic mutations were discovered in the cells of a participant. One of the mutations may carry a remote risk of cancer.
The trial is the first to explore whether cells known as induced pluripotent stem (iPS) cells can be used to treat disease. These are made by taking cells from someone鈥檚 skin and using a cocktail of chemicals to 鈥渞ewind鈥� them to a stem-cell-like state. This means they have the potential to turn into almost any other type of cell, allowing them to be converted into the type required, before being transplanted back.
In this trial, skin cells were turned into retinal cells in an attempt to reverse the damage to eyes caused by age-related macular degeneration, which leads to loss of vision and can cause blindness. The first patient, a 70-year-old woman, was treated last September and is reportedly in good health.
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There is a lot resting on the outcome of the trial. It could finally provide evidence of the clinical potential of iPS cells, which were first created in 2006.
鈥淎 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,鈥� says trial leader of the Riken Center for Developmental Biology in Kobe, Japan.
Analysis of the patient鈥檚 cells revealed six mutations. Three were genes that had been deleted and three were changes to genes, including one in an oncogene 鈥� a gene with the potential to cause cancer, although this one is linked with a low risk. The mutations were not detectable in the original skin cells, suggesting that they occurred as a result of the iPS-cell procedure.
鈥淓ither they were there at undetectable levels in the skin cells, or they were caused by the iPS cell induction process,鈥� says Shinya Yamanaka of Kyoto University in Japan, one of the scientists who developed the reprogramming technique. 鈥淗owever, the risk of carcinogenesis was considered low.鈥�
Another factor has influenced the halting of the trial. Regulatory changes in Japan mean that now only certain types of institution can run stem-cell trials, Takahashi told New 杏吧原创. Once the team has worked out how to accommodate these changes, they hope to resume work and test five more people using healthy, mutation-free skin cells from younger people.
鈥淚 think it鈥檚 an easily fixable problem if they go this route,鈥� says Robert Lanza, chief scientist at Ocata Therapeutics in Marlborough, Massachusetts, which is also developing stem-cell therapies for age-related blindness.
Nonetheless, the discovery of mutations that could be related to the iPS-cell process is disconcerting, and is something that people have worried about since the field鈥檚 infancy. One of the benefits of stem-cell therapies is that the cells can multiply rapidly 鈥� a characteristic shared by cancer cells.
But that similarity doesn鈥檛 necessarily mean cancer will develop. 鈥淚t鈥檚 important to understand that even mutations in oncogenes don鈥檛 guarantee that cancer will result,鈥� says Jeanne Loring of the Scripps Research Institute in La Jolla, California.
鈥淚t will be important to determine the source of the mutation before jumping to conclusions that reprogramming cells will always carry this sort of risk,鈥� says Mike Cheetham of the Institute of Ophthalmology at University College London.
聯It will be important to determine the source of the mutation before jumping to conclusions聰
This article appeared in print under the headline 鈥淯nexpected mutations put stem cell trial on hold鈥�