Science: Induced Pluripotent Stem Cells Possible Without the Genetic Damage

Chimeric mouse used in the study

Image courtesy of Mathias Stadtfeld and Konrad Hochedlinger

Researchers say they have developed a method for generating "induced pluripotent stem cells" (iPS cells) using viruses that do not integrate themselves into the hosts' genome, bypassing a problem that has undermined the success of previous iPS cells. These findings, reported in the latest issue of Science, represent a major step forward in the generation of patient-specific cells for the study of disease and the future application of iPS cells in a clinical setting.

Matthias Stadtfeld from the Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine as well as the Harvard Stem Cell Institute generated this new line of iPS cells along with colleagues. The researchers say that it will be important to determine if human iPS cells generated in the future by this method are as potent as human embryonic stem cells for potential clinical applications.

In general, iPS cells show potential for growing into a variety of other specialized cells, including lung, brain, and heart cells. However, whether or not iPS cells are as useful as embryonic stem cells in clinical applications is still being debated.

Scientists have grown iPS cells that resemble embryonic stem cells, but the process, which involves the introduction of particular DNA-binding proteins to cells via potentially harmful viruses, often altered the cells' genomes and caused tumors in animals. This new finding demonstrates that iPS cells can be grown without the permanent genetic damage previously associated with their design, and Stadtfeld and his colleagues say they have not yet observed any unwanted side-effects.

Pluripotent stem cells induced by transient gene delivery

Image courtesy of Mathias Stadtfeld and Konrad Hochedlinger

The researchers are hopeful. In an email interview, Stadtfeld said previous lines of iPS cells "were all 'tainted' by the presence of potentially harmful viral DNA at random locations in their genome. We were interested in developing a technology that would allow the generation of iPS cells that have no viral integrations. We rationalized that integration-free iPS cells should represent safer patient-specific stem cells, and would also more closely resemble 'traditional' embryonic stem cells."

In the past, reprogrammed cells similar to these iPS cells have been shown to alleviate the symptoms of Parkinson's disease and sickle cell anemia in mouse models, so this new discovery might eventually lead to advances in cell therapy and treatments of human disease as well. However, the future of these iPS cells is uncertain.

"At least two more steps must be taken before therapies based on this iPS cell technology can be devised," Stadtfeld explained. "First, integration-free iPS cells have to be derived from human cells, which is probably only a matter of months away. And secondly, we have to figure out ways to generate transplantable adult tissues from these cells, which appears to be the larger roadblock at the moment."

Stadtfeld's results are published in the 26 September issue of Science, the journal of AAAS.

Brandon Bryn

29 September 2008