Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins, researchers at the Stanford University School of Medicine have found.
The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish.
"We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies," said Marius Wernig, assistant professor of pathology and senior author of the study.
After their success in laboratory mice, Wernig team applied a similar technique to human cells.
They first showed that they could convert human embryonic stem cells to neurons by infecting them with a virus expressing the same combination of proteins: transcription factors called Brn2, Ascl1 and Myt1l. They termed the treatment "BAM" for short.
BAM treatment readily turned the embryonic stem cells into functional neurons within six days. It also worked on induced pluripotent stem cells.
In experiments using skin cells from fetuses and newborns, they found that BAM treatment caused these mature skin cells to look more like neurons, but that the resulting cells were unable to generate the electrical signals that neurons use to communicate with one another.
But after adding a fourth transcription factor called NeuroD, the skin cells then transformed to functional neurons in the laboratory culture dish within about four to five weeks - expressing electrical activity and even integrating into and interacting with mouse neurons grown on a laboratory dish.
The study was published online May 26 in Nature.