A scalable, clinic-friendly recipe for converting skin cells to muscle cells

Way back in 1987, about two decades before Shinya Yamanaka would go on to identify four proteins that can reprogram skin cells into induced pluripotent stem cells (iPSCs), Harold Weintraub’s lab identified the first “master control” protein, MyoD, which can directly convert a skin cell into a muscle cell. Though MyoD opened up new approaches for teasing out the molecular mechanisms of a cell’s identity, it did not produce therapeutic paths for replacing muscle damaged by disease and injury.

That’s because MyoD-generated muscle cells are not amenable to a clinical setting. For a cell therapy to be viable, you need to manufacture large amounts of your product to treat many people. But these MyoD cells do not grow well enough to be effective to serve as a cell replacement therapy. Generating iPSC-derived muscle cells provides the potential of overcoming this limitation but the capacity of the embryonic stem cell-like iPSC for unlimited growth carries a risk of forming tumors after the transplanting iPSC-derived cell therapies into the muscle.

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This image shows iMPCs stained for markers of muscle stem, progenitor and differentiated cells. iMPCs recapitulate muscle differentiation in a dish. Credit: Ori Bar-Nur and Mattia Gerli

A recent study in Stem Cell Reports, by Konrad Hochedlinger’s lab at Massachusetts General Hospital and the Harvard Stem Cell Institute, may provide a work around. The team came up with a recipe that calls for the temporary activation of MyoD in mouse skin cells, along with the addition of three molecules that boost cell reprogramming. The result? Cells they dubbed induced myogenic progenitor cells, or iMPCs, that can make self-sustaining copies of themselves and can be scaled up for manufacturing purposes. On top of that, they show that these iMPCs carry the hallmarks of muscle stem cells and generate muscle fibers when transplanted into mice with leg injuries without signs of tumor formation.

A lot of work still remains to be done, like confirming that these iMPCs truly have the same characteristics as muscle stem cells. But if everything pans out, the potential applications for people suffering from various muscle disorders and injuries is very exciting, as co-first author Mattia FM Gerli, PhD points out in a press release:

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Mattia FM Gerli, PhD

“Patient-specific iMPCs could be used for personalized medicine by treating patients with their own genetically matched cells. If disease-causing mutations are known, as is the case in many muscular dystrophies, one could in principle repair the mutation in iMPCs prior to transplantation of the corrected cells back into the patient.”

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