A possible setback for one stem cell alternative

Scientists developing stem cell therapy have wandered into a minefield of controversy. While embryonic stem cells may eventually be developed into treatments for currently incurable conditions, some portion of the population will always have ethical concerns about the cells' source. But in 2006, it appeared that a compromise had been struck: cells that are derived from adult tissues and treated to revert them to their versatile embryonic state. Even pro-life groups which oppose research into embryonic stem cells have generally embraced this particular alternative. Since then, research into the induced pluripotent stem cells (iPSCs) has furiously tried to turn theory into therapy.

However, two papers published in Nature earlier this month show how much we have to learn about the process of making iPSCs. The first group of these cells was created by using viruses to insert genes into adult skin cells--and one of those genes is known to be involved in cancer. Since then, researchers have tried to make their methods safer, and it seemed to be working. But even now, iPSCs still carry a substantial amount of risk, as Ed Yong explains in Discover magazine:

It’s a notoriously inefficient technique. If you start with 100,000 skin cells, you’d only get a handful of iPSCs at the end of it. Scientists pick these lonely successes and grow them into a large colony again, in which all the cells came from a single ancestor. They repeat the process again and again until they get enough cells.

This is a stressful process for cells. It churns out a lot of highly reactive molecules that charge around and damage DNA as they collide with it. This may explain why Hussein and Batada found a lot of new CNVs [copy number variations, where entire genes are duplicated or deleted] at particularly fragile and exposed parts of the genome.

There’s another problem – by repeatedly growing colonies from small groups of cells, scientists squeeze them through a genetic bottleneck. Any mutations that arose in the cherry-picked cells get a helping hand, and they soon dominate the new population. It might even be that iPSCs with mutations in cancer genes are better at growing, and more likely to be picked by eager geneticists.

This explains why iPSCs contained mutations even if they weren’t created using DNA-infiltrating viruses. Fortunately, this problem also suggests an obvious solution – it may be possible to avoid any genetic changes by creating iPSCs more efficiently. Many groups are on the case. Some are adding accelerating molecules to the mix, while others are changing the environment that they grow the cells in. Yet others are working on ways of screening iPSCs on their quality and usefulness, to pick the best and most-suited cells for the job.

Of course, possible pitfalls exist for all forms of stem cell therapy. The first human trial involving embryonic stem cells began in October 2010, after a months-long delay prompted by concerns over patients' safety, and it is too soon to say whether the trial was successful. For doctors and patients anxiously holding out hope for stem-cell derived cures, it seems that those cures are perpetually "just over the horizon."

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by Matt Feltz (@mattfeltz)