Stem Cells: Skin Deep

Researchers find breakthrough non-viral method for reprogramming skin cells into stem cells

Over the past decade, no topic has been more controversial in the worlds of science, politics, and religion than stem cell research. Of course, the debate has centered over the ethics of harvesting embryonic stem cells to cure degenerative diseases. But researchers at the universities of Edinburgh and Toronto may have solved the problem by devising a method to turn human skin cells into stem cells so that can be safely transplanted into humans.

We know you readers know your stuff, and you're probably thinking, "Wait a minute…didn't someone already figure out how to make stem cells from skin cells?" Yes. Back in 2007, Japanese professor Shinya Yamanaka discovered a way to turn skin cells into induced pluripotent stem (iPS) cells—which act similarly to embryonic stem cells. Yamanaka's method was a huge step toward solving the fiercely controversial debate over stem cell research (because scientists wouldn't have to use embryos). And because Yamanaka used the donor's own skin cells, the iPS cells were a genetic match—meaning they'd be much less likely to be rejected by the donor's immune system than embryonic stem cells might.

But Yamanaka's method came with a complication. To turn skin cells into iPS cells, four specific genes—c-Myc, Klf4, Oct4 and Sox—must be injected into the DNA. Yamanaka injected these genes by using a number of viruses. The problem is that the viruses might mutate, and eventually cause cancer to develop in the tissue grown from iPS cells.

So, for the past few years, the puzzle for stem cell researchers has been based on how to reprogram skin cells into iPS cells without using viruses.

The breakthrough came when two scientists on opposite sides of the Atlantic discovered they'd solved different halves of the same puzzle. In Edinburgh, a team of scientists led by Dr. Keisuke Kaji from the Medical Research Council (MRC) Centre for Regenerative Medicine, successfully injected the four crucial genes in one single fragment of DNA. But Kaji's team also needed to remove the genes after reprogramming the cells—to avoid abnormalities in the cells' development—and they hadn't yet figured out how to do this. Meanwhile, a team led by Dr. Andras Nagy from the University of Toronto developed a reprogramming system that allowed for removing the genes; yet because his team delivered the genes into four different parts of the genome, they hadn't yet figured out how to remove all of them.

By chance, Kaji and Nagy ended up meeting and combined their efforts, using Kaji's system of inserting the genes into one fragment of DNA and Nagy's "footprint-less" removal system. Before this study, non-viral methods for reprogramming skin cells had only worked on mice. This is the first time they've worked on human skin cells.

"It will still take time before these iPS cells can be given to patients," said Sir Ian Wilmut, director of the MRC Centre for Regenerative Medicine, and who also led the team that cloned Dolly the sheep. "But I believe the team has made great progress, and combining this work with that of other scientists working on stem cell differentiation, there is hope that the promise of regenerative medicine could soon be met."