Stem Cells without Side Effects

Researchers have created healthy stem cells from adult cells--no embryo required.

Last year, researchers announced one of the most promising methods yet for creating ethically neutral stem cells: reprogramming adult human cells to act like embryonic stem cells. This involved using four transcription factor proteins to turn specific genes on and off. But the resulting cells, called induced pluripotent stem (iPS) cells for their ability to develop into just about any tissue, have one huge flaw. They're made with a virus that embeds itself into the cells' DNA and, over time, can induce cancer. Now, scientists at Harvard University have found a way to effect the same reprogramming without using a harmful virus--a method that paves the way for tissue transplants made from a patient's own cells.

Safer cells: Recent efforts to create induced pluripotent stem cells have used a virus that integrates itself into the host's DNA and can cause cancer. Now, using fetal liver cells from mice, Harvard researchers have created a line of cells that are virus-free. Credit: Image courtesy of Mathias Stadtfeld and Konrad Hochedlinger

The first generation of iPS cells was created using a retrovirus to insert the four transcription factors into skin cells. Because a retrovirus, by definition, inserts itself permanently into its host's DNA, this ensured that the transcription factors were transferred, but it also led to the propagation of the virus itself. Furthermore, since the virus confers self-renewal capabilities to its new host cell, many believed that the retrovirus might be required for iPS cells to reproduce.

New research by Konrad Hochedlinger and his colleagues at Harvard University, the Harvard Stem Cell Institute, and the MGH Center for Regenerative Medicine shows that a different type of virus--an adenovirus--can make the transfer in mouse cells without permanently integrating itself. The resulting iPS cells can divide indefinitely but show no trace of the virus--just a temporary infection that disappears within a short time. "That means that the four transcription factors themselves are sufficient to induce pluripotency in adult cells," Hochedlinger says.

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Many view the creation of genetically unmodified iPS cells as regenerative medicine's magic bullet. The cells are not derived from embryos, so researchers can circumnavigate the ethical gray areas. And if these cells turn out to be as potent as embryonic stem cells, they could be used to help regrow tissues damaged in conditions ranging from paralysis to Parkinson's disease to diabetes. If they can be grown from a patient's own cells, they could furthermore be transplanted without triggering immune rejection.

Until now, however, creating iPS cells without integrated viruses had been a major hurdle for stem-cell researchers. Although Hochedlinger has overcome that hurdle, he says there is still some distance to travel. While retroviral techniques allow scientists to turn about one in every 1,000 skin cells into an iPS cell, the adenovirus is far less efficient: only one in every 10,000 to 100,000 fetal liver cells can be converted. "It may be that people have tried adenoviruses before but missed the iPS cells because the efficiency is so low," Hochedlinger says. "We ourselves tried to use adenoviruses a year ago, and it didn't work."