Hold the Embryos: Genes turn skin into stem cells

In an advance that could solve many of the ethical and technical issues involved in stem cell research, two groups of scientists have independently converted human skin cells directly into stem cells without creating or destroying embryos.

“We are now in a position to be able to generate patient- and disease-specific stem cells without using human eggs or embryos,” Shinya Yamanaka, leader of one of the research teams at Kyoto University in Japan, said in an e-mail interview.

Preliminary tests show that the newly created cells can develop into nerve cells, heart cells, or any other kind of cell in the body. Previously, only stem cells taken from early embryos had this kind of flexibility, called pluripotency. Scientists have suggested that such embryonic stem cells could be used for learning about genetic diseases, testing new drugs on cells grown in the lab, or growing healthy cells for therapeutic transplantation.

Producing embryonic stem cells has become controversial, however, because the process destroys the embryo.

“[Our] whole procedure doesn’t involve any embryo,” says Junying Yu, leader of the other research group, at the University of Wisconsin–Madison. “This approach is certainly going to get rid of this [ethical] problem.”

The new technique wouldn’t be suitable for medical therapies because it uses viruses to inject genes into the cells’ DNA. Such viruses insert the genes at random locations, sometimes causing mutations that can lead to cancer. Several research groups are working on other ways to deliver genes into the cells, and developing safer techniques to do so shouldn’t be difficult, observes Jeanne F. Loring, a stem cell researcher at the Scripps Research Institute in La Jolla, Calif.

Both research groups used human skin cells called fibroblasts, chosen because they grow rapidly and are easy to obtain. Yamanaka’s group used skin cells taken from a woman’s face, and Yu’s team used cells from a newborn’s foreskin. Acquiring fibroblasts from a patient would require only shallow penetration of the skin.

The research teams each grew samples containing hundreds of thousands of skin cells in a dish, and then used viruses to carry genes into the cells. These genes are active in embryonic stem cells but switched off in skin cells. Each team used a different combination of four genes, but two of the genes—OCT4 and SOX2—were common to both experiments. The genes work by controlling the activity of many others.

After 12 to 25 days, the injected genes had transformed some of the skin cells into cells with all of the key characteristics of embryonic stem cells, the teams report in upcoming issues of Cell and Science.

“If you didn’t know where they came from, you wouldn’t be able to tell the difference between these [cells] and true human embryonic stem cells,” Yu says.

The experiments each produced between 10 and 35 converted cells, called induced pluripotent stem cells. So a single skin sample can produce several stem cell lines.

“This will be the way people” make stem cells, concludes Loring.