Plan for non-embryo stem cell technique suffers setback

A revolutionary technique that promised to turn a patient's skin cells into vital replacement tissue for transplant surgery has suffered a setback that could scupper its wider use in medicine. The technique allowed scientists to make "embryonic" stem cells without using embryos, raising the prospect of humans being able to turn stem cells derived from a flake of skin into specialised tissues such as heart muscle to brain cells.

However, two independent teams of scientists reported yesterday that these so-called induced pluripotent stem (iPS) cells do not behave exactly like the stem cells found in early human embryos that are just a few days old, which are known to be able to develop into any of the scores of specialised human cells.

Stem cells have generated intense interest because of their potential to be used to make replacement parts for the body but the only proven way of generating them safely and successfully has involved the use of embryos, possibly through the "nuclear transfer" process, or cloning, that resulted in Dolly the sheep in 1996.

However, four years ago a Japanese scientist called Shinya Yamanaka showed it is possible to produce stem cells with embryonic-like qualities by tinkering with a few of the key developmental genes. He called them induced pluripotent stem cells.

Many experts believed that iPS cells offered a way out of the ethical dilemma of using human embryos in stem cell research but the latest findings suggest that it is not easy to make iPS cells that have all the characteristics of the "gold standard" stem cells found in early embryos.

The two research teams both found that the iPS they created retained a "memory" of the specialised cells, such as skin, that were used to create them. The researchers effectively found that the iPS cells were not completely reprogrammed back to the early embryonic stage of development, which might cause problems if they were ever to be used in transplant operations. "Induced pluripotent stem cells retain a 'memory' of their tissue of origin – iPS cells made from blood are easier to turn back into blood than, say, iPS cells made from skin cells or brain cells," said George Daley of the Children's Hospital in Boston, who led one of the research teams whose findings are published in the journal Nature.

"These findings cut across all clinical applications people are pursuing and whatever disease they are modelling ... Everyone working with these cells has to think about the tissues of origin and how that affects reprogramming," Dr Daley said.

Konrad Hochedlinger of the Massachusetts General Hospital, who was part of the second study, published in Nature Biotechnology, said it is possible to fade this memory of iPS cells but only by allowing them to divide over and over again. "How faithfully iPS cells can be reprogrammed into a truly embryonic state has been a longstanding question, and we have found that the cell of origin does affect the capacity of iPS cells to differentiate in vitro into particular cell types. But when cultured iPS cells go through many rounds of cell division, they lose that memory," he said.

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