Researchers at Massachusetts General Hospital, Boston, US, have developed a new, safer method for creating induced pluripotent stem cells - (iPS cells) adult cells made to behave like stem cells by inserting four key genes. Previously these genes have been delivered into cells using retroviruses, which can potentially trigger genetic changes leading to cancer, but the new method avoids this by substituting adenoviruses, which replicate themselves by a different mechanism, according to a study published in the journal Science last Thursday.
Mouse embryos into which the adenovirus iPS cells have been inserted have shown no sign of tumours up to the 13-week stage of study, a positive sign for the new technique. The researchers hope that using a virus that doesn't integrate into the cell's DNA will minimise future problems.
'The nice thing about adenoviruses in contrast with retroviruses is they deliver proteins inside the cells but they will never, ever integrate their DNA into the cells', study leader Konrad Hochedlinger, Massachusetts General Hospital and Harvard Medical School, told Reuters.
However, the new technique is at present little more than a proof of concept as the yield of iPS cells is 10 to 100 times lower than the existing retroviral technique, which itself only yields roughly one iPS cell colony for every 1,000-10,000 subject adult cells. The level of yield is so low that it would be infeasible to employ this technique for the production of therapeutic cells. While it remains an important demonstration that retroviruses are not necessary for the reversal of adult cells into their stem cell state, for the moment it does not eclipse the existing retroviral technique pioneered by Shinya Yamanaka in Kyoto last year.
An additional concern is that, though the cells themselves do not have their DNA altered, around eight per cent of the iPS cells lines produced were found to contain unexpected extra chromosomes. The cause of these additional chromosomes is not known, though it is possible that the adenovirus may have caused some cells to fuse. Nevertheless, the risks from these cells are somewhat lower than that from the tumour-inducing cells found with the retroviral technique but they are still cause for some concern.
Trials on human cells are already underway, says Hochedlinger. 'We are in the process already of trying to make integration-free iPS cells in human cells', he told Reuters. 'It is a little trickier because human reprogramming takes a little while longer than mouse reprogramming. If it works, some day doctors may be able to make tailor-made transplants to treat diseases in people by removing a few cells, transforming them in the lab and transplanting the new tissue or organs back in', he added.