Skin biopsies to obtain fibroblasts for reprogramming into human embryonic-like stem cells could soon become a thing of the past. It has now proved possible to induce the epidermal skin cells that cling to a plucked human hair to pluripotency — that is, to become capable of forming any sort of cell in the body.

Researchers are chipping away on two fronts towards the goal of generating pluripotent human stem cells without involving embryos or genetic engineering. In one approach, they are looking for ways to activate pluripotency genes without permanently changing the cell's genome. Recently, a team led by Doug Melton at Harvard University showed that one of the four genes normally required for reprogramming could be replaced by treatment with a small molecule1.

On the other front, stem-cell researchers are searching for cell types that might be more easily 'reprogrammed' to pluripotency than the skin fibroblasts currently used. Some evidence suggests that liver cells and neural stem cells meet this requirement, but these aren't readily obtainable from human volunteers.

Reporting in Nature Biotechnology, Juan Carlos Izpisúa Belmonte at the Salk Institute in La Jolla, California, reports that keratinocytes, a skin cell type attached to hairs simply plucked from the scalp, can be readily reprogrammed2.

The researchers used the formula pioneered by Shinya Yamanaka to reprogram fibroblasts. This required inserting multiple copies of four pluripotency genes for into the keratinocytes. The rates of successful reprogramming were more than 100-fold higher than those typically reported for fibroblasts, and reprogramming the keratinocytes took only about 10 days, as opposed to three weeks or more.

Whereas fibroblasts are found in the middle layer of the skin, keratinocytes occur in the upper layer, where they produce the protein that forms hair and fingernails. Out of several cell types that Belmonte's team investigated, keratinocytes were the easiest to reprogram. Izpisúa Belmonte and his colleagues created KiPS (keratinocyte-derived induced pluripotent cells) from five adults. They fully characterized one line, from a 30-year-old woman, to show it could be differentiated into cardiomyocytes and dopamine-producing neurons.

It's not entirely clear why keratinocytes are easier to reprogram, but compared with fibroblasts the pattern of genes they express (before reprogramming) is more similar to that of genuine human embryonic stem cells.

Reprogrammed cell lines derived from individual patients could be very useful for drug screening or regenerative therapies, but robust, reliable techniques for generating the cells must be established. An accessible, easily reprogrammable cell type could be a fruitful starting place.

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