Published online 25 September 2008 | Nature | doi:10.1038/news.2008.1132


Cell 'rebooting' technique sidesteps risks

Virus reprograms cells without disrupting genome.

stem cellA pluripotent stem cells induced by transient gene delivery.Mathias Stadtfeld and Konrad Hochedlinger

Scientists today announce a major advance in a technology for engineering cells with broad regenerative powers.

Writing in Science1, a team led by biologist Konrad Hochedlinger of Harvard Medical School in Boston, Massachusetts, describes how it transformed mouse tail and liver cells into an embryonic-like state. And unlike other scientists who had previously made such 'induced pluripotent stem cells', or iPS cells, Hochedlinger's team did not use a virus that integrates itself into a cell's genome to 'reboot' the cells. Instead, the team used an adenovirus, which keeps out of a cell's own DNA, avoiding the potential for serious side-effects such as cancer, which might result from viral disruption of a cell's DNA.

The work brings the science of iPS cells one step closer to clinical reality. But it also answers some key biological questions about the cells: "This is a potentially exciting advance, since it gets around the dangers of viral integration into the genome," says Martin Pera, director of the University of Southern California's Institute for Stem Cell and Regenerative Medicine in Los Angeles.

Tailor-made tissues

Scientists are excited about iPS cells because they can theoretically be made from any of an individual's cells, and might therefore be used to tailor-make tissues that match a patient. They are also being used for the study of disease, and avoid the ethical and practical issues surrounding the use of embryonic stem (ES) cells harvested from blastocysts, the hollow balls of cells that form during the early stages of human development . They are also much more readily available than human eggs, which are also being used in one technique to try to reprogram adult cells.

However, many questions remain about the adenovirally reprogramed cells. Some have claimed that the study eliminates the need for work on human ES cells, but Hochedlinger disagrees: "It's much too early to say that — at this point we clearly still need ES cells," he said.

The issue has been a contentious one in the US presidential campaign. Barack Obama has said that iPS cells do not eliminate the need for ES cell research. John McCain's stance has been more vague, while his running mate, Sarah Palin, opposes ES cell work (see 'US election: Questioning the candidates'). Yet Hochedlinger points out that he has not been able to use his technique to reprogram human cells yet, and that even if his lab was able to do so, researchers still do not know whether iPS cells share all of ES cells' powers.

"It is unclear to what extent ES cells and iPS cells are really equivalent to each other, and showing this will require much more work," says Hochedlinger.

Major question

Hochedlinger's team used the adenoviruses to express genes that rebooted the mouse tail and liver cells so that they took on genetic characteristics akin to embryonic stem cells. Like ES cells, the rebooted cells were also able to form teratomas, a type of tumour, containing the three main tissue types of the body, and could develop into all these tissue types when injected into blastocysts that grew into adult mice. The team also showed that the adenoviruses did not integrate into the cells' genomes.

Yet the team's technique is far less efficient than the integrating virus technique, reprograming cells only 0.0001% to 0.001% of the time. Whether this is good enough to work in human cells is now a major question for the field, Pera said: "It will remain to be seen whether these or other non-integrating vectors can produce sufficient levels of reprograming factors in human cells to enable their conversion to iPS cells," he says. 

  • References

    1. Stadtfeld, M. et al. Science doi: 10.1126/science.1162494. (2008).
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