With the addition of four proteins, adult human skin cells can be transformed into neurons over a month-long period. The findings, reported yesterday in Nature, suggest a process that doesn’t require the reprogrammed adult somatic cells called induced pluripotent stem (iPS) cells.
The method may make it easier to produce patient- or disease-specific neurons for study.
“We are now much closer to being able to mimic brain or neurological diseases in the laboratory,” said School of Medicine assistant professor and lead researcher Marius Wernig in a press release.
He expressed hope that one day the cells could be used for human therapies.
The researchers showed they could convert human embryonic stem cells to neurons by infecting them with a virus that expressed the same proteins used in the study. This treatment, nicknamed “BAM” after an acronym of the three proteins, converted the embryonic stem cells into functional neurons within six days. The same treatment worked on iPS cells, but the process is labor-intensive and relies on cell lines that likely aren’t as diverse as a natural population.
The challenge was to do the same for skin cells without stem cells as an intermediary. The researchers found that BAM treatment to skin cells from fetuses and newborns didn’t have the same effect as it did on the stem cells. The addition of a fourth protein, called “NeuroD,” was the tipping point; it triggered the skin cells’ transformation into functional neurons within about four to five weeks. The cells expressed electrical activity characteristic of neurons and even integrated and interacted with mouse neurons on a laboratory dish.
In 2010, the same research group showed that a similar method worked on mouse skin cells, although it works much less efficiently with human cells. While they found that approximately 20 percent of mouse skin cells transform directly into functional neurons, under current culture conditions only about two to four percent of human skin cells do the same.