Researchers in the UCLA Department of Microbiology, Immunology and Molecular Genetics have developed a novel means of generating adult skeletal muscle-equivalent myofibers from human pluripotent stem cells.
Thousands of people a year are diagnosed with various muscle diseases including neuromuscular disorders, muscular dystrophies, and diseases resulting from metabolic and mitochondrial defects. Generating adult muscle fibers in vitro would allow research surrounding these diseases to more quickly discover therapies and treatments. However, to date no protocol has been identified which generates multinucleated, adult skeletal muscle-equivalent myofibers in vitro. Currently the best protocols used generate mononuclear embryonic muscle cells which are not equivalent to adult skeletal muscle.
Professor Pyle and colleagues have identified a novel protocol for generating adult skeletal muscle equivalent myofibers in vitro from human pluripotent stem cells using a TGF-beta inhibitor. Following cues active during early human muscle development and utilizing the TGF-beta inhibitor, the myofibers generated are multinucleated, express dystrophin, and equivalent to adult skeletal muscle. Additionally, these adult myofibers provide the appropriate niche for skeletal muscle progenitor cells.
Human pluripotent stem cells, adult myofiber, in vitro muscle disease model, directed differentiation, small molecule inhibitor, TGF-beta