Induced Progress

When James Thomson’s and Shinya Yamanaka’s research teams published their ground-breaking papers last year on induced pluripotent stem cells, or iPS cells, one of the major hurdles to clinical application was the propensity of the cells to cause cancer. In these original methods, genetic factors inserted into somatic cells by way of retroviruses induced both pluripotency and caused tumors.

Now, scientists from Harvard University have successfully introduced the pluripotency-inducing genes into mouse somatic cells by way of adenoviruses, which are less harmful than retroviruses because they do not permanently integrate the genes into the cell’s DNA. The study detailing the work was published online yesterday on the website of Science. In its story on the discovery, the The Washington Post quotes Robert Lanza of Advanced Cell Technology, who explains, “The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell. You can’t tell the virus was ever there.” However, the Post also quotes Rudolf Jaenisch of the Whitehead Institute, who expressed doubts about the method, saying, “It’s still very inefficient.”

Indeed, according to the article in Science, the efficiency was “extremely low, ranging from less that 0.0001 to 0.001%,” and that “[t]his frequency is lower than that obtained with integrating viruses (~0.01 to 0.1%) and is probably due to the fact that many cells do not maintain viral expression long enough to trigger entry into a state sustained by endogenous pluripotency factors.”

In order to increase the efficiency of this method of inducing adult cells to become pluripotent, scientists may need to supplement the genes with chemical compounds, as has been done with retroviral reprogramming. At the end of the article in Science, author Konrad Hochedlinger and his research team acknowledge, “Before translating these observations into a therapeutic setting, however, it will be important to asses if human iPS cells generated without viral integration are indeed as potent as human ES cells.”

And that’s one more reason that human embryonic stem cells remain the gold standard of pluripotency, and will still be critical to this ongoing research in regenerative medicine, despite conservative naysayers.

Tags: stem cells

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