Less risk. Adult mouse cells were reprogrammed to an embryonic state without potentially cancer-causing viruses.

Image courtesy of Matthias Stadtfeld and Konrad Hochedlinger

A New, Improved Stem Cell Recipe

Working with mouse cells, scientists have found a safer way to convert adult stem cells into an embryonic state. The standard method to create so-called induced pluripotent stem (iPS) cells relies on potentially cancer-causing retroviruses. In the new approach, a team has substituted safer viruses that could make the cells easier to study and less risky for transplant. The advance raises hopes that researchers will be able to fully capture the potential of iPS cells--and avoid the ethical quandaries that come from working with cells from human embryos.

Many stem cell researchers have high hopes for iPS cells. They dream of a source of pluripotent cells--cells that can become any kind of tissue--without the ethical, practical, and legal tie-ups that have plagued work with embryonic stem cells. Already, groups around the world have made dozens of iPS cell lines derived from patients with hard-to-study diseases (ScienceNOW, 7 August). But the cells have had a major problem: They are made using retroviruses that insert themselves into the cell's genome, potentially in regions that can later trigger cancer. In one experiment, about 20% of chimeric mice made with iPS cells developed tumors. Researchers also worried that the permanently inserted genes might affect the cells' ability to differentiate into mature tissues.

Developmental biologists Matthias Stadtfeld, Konrad Hochedlinger, and their colleagues at Harvard University and Harvard Medical School in Boston have now sidestepped the problem by using a different kind of virus to trigger the production of the proteins that reprogram the cell. Adenoviruses, which cause colds, have the same benefits here as retroviruses, infecting cells and prompting them to produce proteins. But they do not insert themselves into a cell's DNA. In a paper published online yesterday in Science, the researchers reported that they had reprogrammed mouse liver cells into embryolike cells that they call adeno-iPS cells. Like regular iPS cells, these seem to behave like stem cells derived from embryos, but they have not caused tumors in experimental mice.

This isn't a panacea, however. The process is much less efficient than the previous recipe, with reprogramming taking more than a month, compared with 10 or 15 days using retroviruses, Hochedlinger says, and far fewer iPS colonies result from each experiment. That means it might prove difficult to get the technique to work in human cells, because reprogramming them already takes longer and is less efficient than making mouse iPS cells. Hochedlinger says his team has tried the technique in human cells, so far without success.

Those drawbacks mean "there is still quite a way to go" before the new approach can compete with the original recipe, says Lorenz Studer of Memorial Sloan-Kettering Cancer Center in New York City. Studer also points out that adenoviruses, which can cause strong immune reactions, might raise safety questions of their own. But the work is “the first crucial proof-of-concept” that getting around the integrating viruses is possible, he says. "This is just the beginning of a wave of studies" creating second-generation iPS cells, he predicts.

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