Editorial: “Keep stem cell options open“

Hopes that people might one day be given transplants made from their own cells have been dashed by experiments trying out the same procedure in mice.

The mice rejected transplants of stem cells even though they had been generated from skin cells genetically identical to their own.

The surprise finding casts doubt on claims that so-called induced pluripotent stem cells generated from a person’s own tissue will ever be medically useful.


Ever since Shinya Yamanaka at Kyoto University in Japan made iPS cells by reprogramming skin cells in 2006, scientists have hoped that the technique could be used to generate transplantable tissue from an individual’s own cells .

However, the new experiments show that mice recognise many of the reprogrammed cells as foreign and reject them.

“In the context of human therapy, we can’t assume that these iPS cells will be immuno-tolerated,” says Yang Xu at the University of California in San Diego, head of the team.

Xu and his colleagues made the iPS cells from skin cells of genetically identical mice by two methods. The first involved using a virus to ferry four reprogramming genes into each skin cell. These turned the cells into iPS cells, which were then transplanted back into genetically identical mice.

In the second, milder method, Xu’s team introduced the reprogramming factors that the four genes code for without using a virus. They did this by immersing the cells in a solution containing the factors, which entered the cell through a process called electroporation – the use of an electric current to open up channels in the cell membrane .

The transplants produced with a virus were rejected faster and more vigorously than those produced with the milder method. “Damage to the transplanted tissues was much more limited, with only a small number of cells rejected, whereas with the viral method, the damage was extensive,” says Xu.

The reason for rejection turned out to be proteins produced by the iPS cells. One especially strong trigger for rejection was Oct4, one of the reprogramming factors used to turn skin cells into iPS cells. The researchers found that it is subsequently produced by many of the reprogrammed iPS cells .

Xu says that humans and mice are naturally programmed to reject cells that produce Oct4, because the protein is normally only produced fleetingly during embryonic development and could be dangerous if produced in adult organisms. The reason rejection of the virally produced iPS cells was stronger was because as the gene coding for Oct4 remained switched on long after the reprogramming had finished.

Xu says that a possible solution for the milder method is to screen cells before they are transplanted to check whether they are producing the factors that cause rejection. A better solution would be to fine-tune the process to eliminate these unwanted effects.

“It’s important to continue pursuing treatments based on human embryonic stem cells as these have so far proved to be the most reliable and versatile for regenerating new cells and tissue,” says Xu.

Some people who oppose research on human embryonic stem cells (hESCs) claim that research on them should be halted because iPS cells are just as versatile but can be obtained without destroying embryos. The new research shows that iPS cells might not be the answer after all.

“Xu’s findings throw another obstacle in the way of iPS cell development,” says Robert Lanza, chief scientist at Advanced Cell Technology of Worcester, Massachusetts, which has won approval to test cell treatments derived from hESCs against two forms of blindness.

Journal reference: Nature, DOI: 10.1038/nature10135