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Engineers grow functioning human muscle from skin cells

First functioning human muscle grown from induced pluripotent stem cells holds promise for cellular therapies, drug discovery and studying rare diseases

Duke University




"Starting with pluripotent stem cells that are not muscle cells, but can become all existing cells in our body, allows us to grow an unlimited number of myogenic progenitor cells," said Nenad Bursac, professor of biomedical engineering at Duke University. "These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell."



As the cells proliferated they became very similar to --but not quite as robust as -- adult muscle stem cells. While previous studies had accomplished this feat, nobody has been able to then grow these intermediate cells into functioning skeletal muscle.

The Duke researchers succeeded where previous attempts had failed.

"It's taken years of trial and error, making educated guesses and taking baby steps to finally produce functioning human muscle from pluripotent stem cells," said Lingjun Rao, a postdoctoral researcher in Bursac's laboratory and first author of the study. "What made the difference are our unique cell culture conditions and 3-D matrix, which allowed cells to grow and develop much faster and longer than the 2-D culture approaches that are more typically used."




The pluripotent stem cell-derived muscle fibers develop reservoirs of "satellite-like cells" that are necessary for normal adult muscles to repair damage, while the muscle from the previous study had much fewer of these cells. The stem cell method is also capable of growing many more cells from a smaller starting batch than the biopsy method.


"The prospect of studying rare diseases is especially exciting for us," said Bursac. "When a child's muscles are already withering away from something like Duchenne muscular dystrophy, it would not be ethical to take muscle samples from them and do further damage. But with this technique, we can just take a small sample of non-muscle tissue, like skin or blood, revert the obtained cells to a pluripotent state, and eventually grow an endless amount of functioning muscle fibers to test."

The technique also holds promise for being combined with genetic therapies. Researchers could, in theory, fix genetic malfunctions in the induced pluripotent stem cells derived from a patient and then grow small patches of completely healthy muscle. While this could not heal or replace an entire body's worth of diseased muscle, it could be used in tandem with more widely targeted genetic therapies or to heal more localized problems.



This work was supported by National Institutes of Health (UH3-TR000505, UG3-TR002142, AR065873, and AR070543).

CITATION: "Engineering Human Pluripotent Stem Cells Into a Functional Skeletal Muscle Tissue." Lingjun Rao, Ying Qian, Alastair Khodabukus, Thomas Ribar and Nenad Bursac. Nature Communications, January 2018. DOI: 10.1038/s41467-017-02636-4
