The team’s first attempt had been with skin cells. Upon hearing that liver cells required less viral integration for effective reprogramming, however, they changed their approach.
The efficiency, as described in latest edition of the journal Science, is still incredibly low. Out of 1 million adenovirus-infected cells, the researchers ultimately produced just one stable line of stem cells. But the line was genetically unaltered, and when the cells were implanted in mice, they formed a cluster of cells that had differentiated into multiple tissue types (a standard test for pluripotency). When the researchers injected the cells into mouse embryos, the resulting mice had integrated the stem cells into a number of different types of tissue, including tissue in the brain, lungs, and heart. And mice as old as 13 weeks remained tumor-free.
Until now, iPS cells couldn’t be compared to embryonic stem cells, since the effects of the integrated virus were unknown. “It was like comparing apples and oranges,” Hochedlinger says. Now, however, the potency of the two cell types can be evaluated head to head. “You can really think about doing this in a human setting now, and about making genetically unmodified human cells for modeling or even for therapy.”
The finding already has other stem-cell experts thinking about the possibilities. “The paper represents a major breakthrough in reprogramming research and proves to the field that we can reprogram cells directly without viral contamination,” says George Daley, a Harvard biologist and stem-cell researcher who was not involved with the research. “It is a major step towards making clinical transplantation of patient-specific cells feasible.”
Hochedlinger and his colleagues are now working to increase the efficiency of their adenovirus technique and to repeat their methods to create human iPS cells. “Once we do that,” Hochedlinger says, “we can figure out whether [embryonic stem] cells and unmodified iPS cells are really identical to each other or not. I don’t know the answer yet.”