Researchers have grown the first functioning human skeletal muscle from induced pluripotent stem cells. The ability to start from cellular scratch using non- muscle tissue will allow scientists to grow far more muscle cells, researchers said. It will provide an easier path to genome editing and cellular therapies, and develop individually tailored models of rare muscle diseases for drug discovery and basic biology studies, they said. "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 at Duke University in the US. "These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell," said Bursac. The researchers started with human induced pluripotent stem cells. These are cells taken from adult non-muscle tissues, such as skin or blood, and reprogrammed to revert to a primordial state. The pluripotent stem cells are then grown while being flooded with a molecule called Pax7 - which signals the cells to start becoming muscle. 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. "It has 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 3D matrix, which allowed cells to grow and develop much faster and longer than the 2D culture approaches that are more typically used," said Rao. Once the cells were well on their way to becoming muscle, Bursac and Rao stopped providing the Pax7 signalling molecule and started giving the cells the support and nourishment they needed to fully mature. The researchers implanted the newly grown muscle fibres into adult mice and showed that they survive and function for at least three weeks while progressively integrating into the native tissue through vascularisation. The resulting muscle, however, is not as strong as native muscle tissue, and also falls short of the muscle grown in the previous study that started from muscle biopsies, researchers said. Despite this caveat, the researchers say this muscle still holds potential that the stronger, older relative does not.
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