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iPS cells match embryonic stem cells in disease-modeling smackdown

Seizing on the serendipitous finding of a human embryo carrying a genetic condition known as Marfan syndrome, an all-star team of Stanford scientists led by Mike Longaker, MD, pitted induced pluripotent stem cells (iPS cells for short) against embryonic stem cells and showed that the former mirror Marfan at the cellular level every bit as well as the latter do. This bodes well for the use of iPS cells for personalized medicine.

Breakthrough - a term that should not be tossed around lightly - is the right word choice for iPS cells' discovery by Shinya Yamanaka, MD, PhD, in 2006. Derived in a dish from fully differentiated tissues such as skin (which is one hell of a lot easier to get hold of and work with than embryos), these cells closely mimic embryonic stem cells (ESCs) in their ability to differentiate into every one of the 200-odd cell types occurring in our bodies, or alternatively to rest content, replicating placidly in the petri plate where they were produced, until duty calls.

The proliferative potential and protean plasticity of ESCs and iPS cells alike render them promising prospects for regenerative medicine: differentiation of such cells into one or another tissue of choice, then popping this new material into place as a substitute for the spent, injured or defective tissue of an ailing patient. That's going to be a long, long way off.

But because iPS cells can be derived from essentially anyone through relatively noninvasive means, they offer a much more near-term, low-cost kicker: The tissues into which they differentiate carry precisely the same genetic background as those of the person they came from. You wouldn't want to go drilling into a person's heart or brain for a tissue sample; you'd even think twice before probing the liver, pancreas, or other internal organs for a biopsy. But with iPS cells, you don't have to. They can be coaxed in vitro into becoming cell types that, in the patient/donor, are malfunctioning. Then they can be studied with all the analytical tools of modern bioscience. In principle, they can also be used for in vitro assays screening thousands or tens of thousands of drugs, to see which drugs best rectify or at least mitigate that particular patient's problem.

But are iPS cells the sparkling surrogates for their more problematic and technically finicky counterparts, the hESCs, that many experts believe them to be? Or are they instead dubious doppelgangers, doomed to deliver a distorted reflection of natural tissues and whatever disease they may be packing? Does iPS cells' sorcery-like summoning (via a witches' brew of transcription factors to coax initially differentiated cells back to an ESC-like state) leave them too artifact-ridden to accurately mirror those maladies?

The new study suggests that the answer is no. The iPS cells made from the skin of Marfan patients matched ESCs derived from a Marfan-syndrome-carrying embryo in their ability to mirror Marfan's defining features: a pronounced proclivity to form cartilage at the expense of bone.

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