Scientists have managed to reprogram human skin cells directly into cells that look and act like embryonic stem (ES) cells. The technique makes it possible to generate patient-specific stem cells to study or treat disease without using embryos or oocytes--and therefore could bypass the ethical debates that have plagued the field. "This is like an earthquake for both the science and politics of stem cell research," says Jesse Reynolds, policy analyst for the Center for Genetics and Society in Oakland, California.
The work builds on a study published last year by Shinya Yamanaka of Kyoto University in Japan, which showed that mouse tail cells could be transformed into ES-like cells by inserting four genes (ScienceNOW, 3 July 2006). Those genes are normally switched off after embryonic cells differentiate into the various cell types. In June this year, Yamanaka and another group reported that the cells were truly pluripotent, meaning that they had the potential to grow into any tissue in the body (ScienceNOW, 6 June).
Now the race to repeat the feat in human cells has ended in a tie: Two groups report today that they have reprogrammed human skin cells into so-called induced pluripotent cells (iPCs). In a paper published online in Cell, Yamanaka and his colleagues show that their mouse technique works with human cells as well. And in a paper published online in Science, James Thomson of the University of Wisconsin, Madison, and his colleagues report success in reprogramming human cells, again by inserting just four genes, two of which are different from those Yamanaka uses.
In the new work, Yamanaka and his colleagues used a retrovirus to ferry into adult cells the same four genes they had previously used to reprogram mouse cells: OCT3/4, SOX2, KLF4, and c-MYC. They reprogrammed cells taken from the facial skin of a 36-year-old woman and from connective tissue from a 69-year-old man. Roughly one iPC cell line was produced for every 5000 cells the researchers treated using the technique, an efficiency that enabled them to produce several cell lines from each experiment.
Thomson's team started from scratch, identifying its own list of 14 candidate reprogramming genes. Like Yamanaka's group, the team used a systematic process of elimination to identify four factors: OCT3 and SOX2, as Yamanaka used, and two different genes, NANOG and LIN28. The group reprogrammed cells from fetal skin and from the foreskin of a newborn boy. The researchers were able to transform about one in 10,000 cells, less than Yamanaka's technique achieved, Thomson says, but still enough to create several cell lines from a single experiment.
Although promising, both techniques share a downside. The retroviruses used to insert the genes could cause tumors in tissues grown from the cells. The crucial next step, everyone agrees, is to find a way to reprogram cells by switching on the genes rather than inserting new copies. The field is moving quickly toward that goal, says stem cell researcher Douglas Melton of Harvard University. "It is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes" and produce reprogrammed cells without genetic alterations, he says.
Once the kinks are worked out, "the whole field is going to completely change," says stem cell researcher Jose Cibelli of Michigan State University in East Lansing. "People working on ethics will have to find something new to worry about."
For a more in-depth news story on this topic, see this week's issue of Science, available online 22 November.