Stem cells and controversy often seem inextricably linked. Recent advances in generating so-called 'induced pluripotent stem cells' (iPS cells) have helped address some critics' concerns, as these cells are not derived from embryonic tissue. However, many experts still fear that the viruses used to transform regular cells into iPS cells could turn rogue and cause uncontrolled changes, such as cancer.

Now scientists have developed a new way to generate iPS cells that potentially avoids the viral hazards thought to plague these stem cell lines. Matthias Stadtfeld of the Harvard Stem Cell Institute in Boston and his teammates used a heavily modified version of the common cold virus (the adenovirus) to completely override the genetic program of liver and connective tissue cells taken from adult mice, causing those mature cells to revert to an embryonic state (Science, doi: 10.1126/science.1162494; 2008).

Their technique involves trimming the adenovirus down to just the piece needed to transfer the key transcription factors required for genetic reprogramming to the mouse cell, creating a viral vector that serves only as a shuttling tool. This approach renders the virus unable to integrate into the mouse cell genome or replicate on its own. The viral vectors are even lost from the cell over time. Other stem cell lines rely on viruses such as retroviruses that integrate permanently into the host cell's genome—an undesirable effect.

Stadtfeld notes that this method of creating iPS cells works better in liver cells than in fibroblasts, which generate connective tissue and are commonly used by stem cell researchers. One reason for this may be that adenoviruses infect liver cells more easily.

At this point, the method is still a research tool. Stadtfeld says, “In principle, there is no reason why we can't use this technology to generate this type of stem cell in human cells, and this is likely to be done in the next six to twelve months.” In the short term, Stadtfeld hopes to use these cells for drug screening and, in the long term, to treat genetic diseases, such as sickle cell anemia.

The adenovirus approach represents one of a growing number of attempts to make safer iPS cells. A paper published in October suggested that exposing skin cells to a chemical—valproic acid—could reduce the number of genes that the cells need to receive to revert to iPS cells (Nat. Biotechnol. doi: 10.1038/nbt.1502; 2008).