A Better Way to Make Embryonic-like Stem Cells

Scientists in Canada and Scotland have developed a virus-free method for generating embryonic-like stem cells that does not involve destroying embryos. Scientists say the new approach to growing so-called induced pluripotent stem (iPS) cells is an important step toward creating safe and reliable populations of cells for research and therapy.

To create iPS cells, researchers turn back the clock in mature cells. They do this by reactivating dormant genes associated with pluripotency--a primitive state in which a cell has the potential to become any cell type in the body. Scientists first introduced iPS cells in 2006 and since then have been ironing out the kinks in how to make them. For example, viruses are ordinarily used to ferry in genes to activate pluripotency, but this foreign DNA integrates into the genome, and experts worry that it might disrupt development or cause cancer.

Over the past year or so, various scientists have reported improvements on the technique, using fewer genes and safer viruses, or plasmids--chunks of DNA containing the necessary factors to activate pluripotency. But alternative approaches, although safer, are often much less efficient.

Now, two groups say they've developed a strategy that accomplishes two goals: it dispenses with the viral vector, and it rids a cell completely of the introduced genes after they have done their job. The groups--one headed by stem cell researcher Keisuke Kaji of the University of Edinburgh in the United Kingdom and the other by developmental biologist Andras Nagy of the University of Toronto in Canada--decided to work together after discovering that each was developing a solution to a different aspect of the problem.

The work involves using an engineered chunk of DNA instead of a virus to introduce factors into a cell that will turn on genes needed for pluripotency. Nagy explains that the team used "mobile DNA elements" called transposons that jump from one place to another in the chromosome. Although fragments of DNA called plasmids have been tried for the same purpose, Nagy says this is the first time a nonviral method has worked with human cells. What's more, he says, the team "took advantage of the other property" of the system, which was that it could be mobilized via an enzyme, transposase, to effect the "seamless removal" of the foreign DNA without disrupting the newly gained pluripotency. So far, the teams have removed the genes in only mouse cells, but they soon expect to show it can also be done with human ones. Both teams publish their findings online this week in Nature.

Shinya Yamanaka, the Kyoto University researcher who authored the original report of iPS cells, says "the transposon-based system seems simple and powerful" and "should be extremely useful in understanding molecular events during iPS cell generation."

Stem cell researcher Konrad Hochedlinger of Harvard University, who last year reported using a safer type of virus to generate iPS cells agrees that "these papers are an important advance." But he says "it remains unclear which treatment will be the best to produce iPS cells."

Hochedlinger and others warn that despite the lightning speed at which stem cell science is progressing, until scientists have a sure-fire method for creating ES-like cells, they still need to be able to work with the "gold standard" for pluripotent cells: cells from human embryos.