A team of biomedical engineers have made a breakthrough in cell therapy research by successfully growing the first functioning human skeletal muscle from induced pluripotent stem cells. Previous related work resulted in the growth of skeletal muscle from primary human myoblasts obtained from muscle biopsies. However, primary cells are not the optimal starting material since they have limited growth in vitro, are less robust with serial passaging, and can be difficult to get from donors. Human pluripotent stem cells (hPSCs), which do not have these limitations, show promise for regenerative therapy applications. The research findings were published in Nature Communications.
"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."
Through trial and error, the team developed a reproducible protocol utilizing overexpression of Pax7, a myogenic transcription factor, to differentiate hPSCs into induced myogenic progenitor cells (iMPCs). The researchers demonstrated that in 2D culture, iMPSCs spontaneously differentiate into contacting multinucleated myotubes. Additional studies involving 3D culture showed that iMPSCs form functional skeletal muscle tissues (iSKM bundles) that behave like muscle fibers. The iSKM bundles were then implanted into mice and were observed to survive for at least three weeks and integrate into native mouse muscle tissue.
Although the new muscle tissue is not as strong as native tissue or muscle grown from adult cells, researchers believe it has therapeutic potential. The stem-cell derived tissue has a large population of “satellite-like cells” that help adult muscles repair damage. Also, many more cells can be grown via the stem cell method than from adult cells and a much smaller number of cells are required to start the differentiation process. The research team is now focused on growing stronger muscle tissue with the hope of developing mouse models of rare muscle diseases and using the new method for regenerative therapies.