“Biomedical engineers have grown the first working human skeletal muscle from induced pluripotent stem cells.
The advance builds on work published in 2015 when researchers grew the first functioning human muscle tissue from cells obtained from muscle biopsies. The ability to start from cellular scratch using non-muscle tissue will allow scientists to grow far more muscle cells, 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.
“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,” says 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.”
In their previous work, Bursac and his team started with small samples of human cells obtained from muscle biopsies, called “myoblasts,” that had already progressed beyond the stem cell stage but hadn’t yet become mature muscle fibers. They grew these myoblasts by many folds and then put them into a supportive 3D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning human muscle fibers.
In the new study, the researchers instead 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.
The 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,” says 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…” – Excerpt from futurity.org posted by Ken Kingery-Duke.