In Situ Cellular Reprogramming Offers a New Avenue for Repair of Neuronal Circuitry

Therapeutic approaches for ALS based on stem cell transplantation into the spinal cord have shown promise, and are already being tested in the clinic (see, for example, recent news). The beneficial effects of the transplanted cells appear to be mediated primarily by production of trophic factors and reduction of inflammation and astrogliosis. However, efforts to repair dying motor neurons have proven challenging, as the transplanted cells often fail to extend long axonal projections and integrate into the complex motor neuronal circuitry. A new proof of concept study from Chun-Li Zhang’s group at University of Texas Southwestern Medical Center in Texas, published February 25 in Nature Communications, demonstrates that resident astrocytes in the spinal cord can be reprogrammed by expression of SOX2 into doublecortin-positive neuroblasts. These stem cells gradually differentiate into motor neurons in the spinal cord, and exhibit electrophysiological activity indicative of synapse formation. These findings open a new avenue for replacing damaged motor neurons in ALS by in situ reprogramming of endogenous astrocytes. Further research is needed to determine whether the newly-generated motor neurons are able to improve motor function following injury or disease. To read more about their approach and the remaining open questions, click here.

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