CIRM grantees convert skin to nerve precursors

A new paper from grantees at Stanford University School of Medicine reports an advance in directly converting one adult cell type to another. This paper, out of Marius Wernig’s lab, builds on his previous work converting mouse skin cells and then human skin cells into nerve cells.

In recent years, a handful of researchers have managed to convert on adult cell type direct into another mature cell type, bypassing the need to reprogram the cells to an embryonic-like state. This technology is still a long way from being ready for therapies (as you can read about in our blog here). Still, the technique suggests the possibility of one day directly converting a cell in the body into a type that’s needed to repair damage, or of creating replacement cells in the lab.

In this latest installment, Wernig and his group converted mouse skin cells into a precursor to nerves called the neural precursor cell. This may sound like a relatively small difference over previous work, but the implications are big.

A press release from Stanford describes this advance:

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

“We are thrilled about the prospects for potential medical use of these cells,” said Marius Wernig, MD, assistant professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “We’ve shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy.”

Back in July we blogged about Wernig’s work and the time it takes to turn these types of advances into new therapies. (You can read that blog here.) We’ve also written about related work by CIRM grantee Deepak Srivastava, who is director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco (here’s more on his work). Stanford quotes Srivastava commenting on Wernig’s work:

“Dr. Wernig’s demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury. It also suggests that we may be able to transdifferentiate cells into other cell types.”

CIRM funding: Ernesto Lujan (TG2-01159)

A.A. Lujan, E., Chanda, S., Ahlenius, H., Sudhof, T., & Wernig, M. (2012). Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1121003109