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Stem Progress

Science and Cell logosResearchers working independently in Japan and the U.S. published papers this week announcing the creation of non-embryonic pluripotent stem cells. A team led by Shinya Yamanaka from Kyoto University and another led by James Thomson from the University of Wisconsin-Madison presented their work in Cell and Science, respectively announcing their discovery of induced Pluripotent Stem (iPS) Cells.

What makes iPS cells special is the fact that they were created from somatic cells. Specifically, Yamanaka used facial skin cells and connective tissue cells from joints, Thomson used fetal fibroblast cells, and both used neonate foreskin cells. Both teams then used retroviruses to insert copies of four new genes into these cells, thereby reprogramming them with the ability to differentiate into any of the over 200 cell types found in the human body. This method side-steps the ethical concerns of those who object on moral or religious grounds to harvesting pluripotent embryonic stem cells from human embryos, which destroys the embryos. This approach also allays the ethical concerns of those who fear that women could be exploited for their eggs which would then be used to clone embryos and harvest stem cells.

Moreover, research on iPS cells would be eligible for federal funding, unlike embryonic stem cells. James Battey, vice-chairman of the NIH’s stem cell task force told the Washington Post today,”I see no reason on Earth why this would not be eligible for federal funding.”

Regardless of the ethical concerns, these discoveries represent a major scientific breakthrough, revealing that somatic cells are much more malleable than previously thought. The Washington Post also reports that Yamanaka was able to coax the iPS cells into becoming nerve cells and beating heart cells. Moreover, these new cells are genetic matches to the donor cells, meaning they could replace or repair the donor’s tissue without risk of rejection.

Both teams used retroviruses to introduce the new genes into the skin cell genomes. This method is far simpler than Somatic Cell Nuclear Transfer, which replaces the entire genome of an egg. Dr. Yamanaka tells the Wall Street Journal that, “Any scientist with basic technology in molecular and cell biology can do reprogramming.”

Both teams used dangerous viruses to transplant the genes into the skin cells, but Yamanaka and other scientist are testing other non-harmful viruses and are confident that a safe method of gene transfer is close at hand. The retroviruses could also cause tumors in tissues grown from the cells, so the best reprogramming method might be one that switches on a cell’s existing genes for pluripotency rather than insert new genes. Harvard University’s Douglas Melton tells ScienceNow that, “it is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes,” which would produce reprogrammed cells without genetic alterations. Robert Lanza of Advanced Cell Technologies in MA tells NewScientist that, “The FDA would never allow us to use these virally modified cells in patients.”

Despite being nearly identical, the iPS cells still differ from real embryonic stem cells (ESCs). Yamanaka states in the Cell article that, “DNA microarray analyses showed that the global gene-expression patters are similar, but not identical between human iPS cells and hES cells.” So embryonic stem cells are still the gold standard against which researchers will have to measure any new cells pluripotent cells. However, in an interview with the LA Times, Yamanaka admits, “‘Even if there are subtle differences…I don’t think they have to be identical’ to embryonic stem cells to be useful in medical applications.”

Thomson explained the SCNT/ESC issue to MSNBC’s Alan Boyle:

Yeah, my feeling is that somatic cell nuclear transfer was an experimental technique, and it could have led to a mechanistic understanding of how reprogramming could occur. But I was skeptical that it could ever enter the clinic because of practical reasons.

This may not be the end of the story. These pluripotent cells may not be perfectly like embryonic stem cells. We don’t know yet. But I do think this is the path that people are going to follow now.

Tackling the bioethical implications of the discoveries, Science Progress advisory board member Art Caplan argues that, “it is a bit too soon to stop working on cloning as a technique to generate stem cells.” He admits that “even though these announcements are momentous, until a reprogrammed panacea cell is used to make stem cells that actually function properly to repair a damaged nerve, spinal cord or heart, all avenues of research must be funded and pursued.”

Yuval Levin notes on the National Review Online that the political controversy should be put aside and credit should be given where it’s due: “It’s the scientists’ extraordinary work—and not the politicians—that really made this possible. This is not a win for one side or the other.”

Thomson told CNNMoney: “I believe that these results, while they don’t eliminate the controversy, are probably the beginning of the end of the controversy.”

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