Adult human muscle tissue harbors a population of unusual progenitor cells that can regenerate skeletal muscle more effectively than other known muscle progenitor cells. These cells could expand options for researching and treating diseases like muscular dystrophy and may offer a potential strategy to identify progenitor cells in other tissue.

Johnny Huard, Bruno Péault and colleagues from the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, Pennsylvania report the discovery of these cells in Nature Biotechnology1. Like other so-called multi-lineage cells, the cells can differentiate into a variety of tissues in the laboratory, including muscle, bone and cartilage, but these cells can also be readily identified, purified and cultured from adult tissue — a strategy that has so far eluded researchers working with other multi-lineage adult stem cells. Termed myoendothelial cells by the research team, these cells express proteins that are typical of both muscle cells and endothelial cells.

The cells reside in the interstitial spaces between muscle fibres, where blood vessels, which are lined by endothelial cells, are abundant. When purified and injected into damaged muscle in immunodeficient mice, myoendothelial cells generated 10 times more muscle fibres than injected endothelial cells did and 18 times as many as did myogenic cells, also known as satellite cells. Though not as effective as freshly collected cells, myoendothelial cells that had been cultured for up to 6 weeks could still regenerate muscle. New myofibres persisted up to 4 months after transplantation.

Moreover, myoendothelial cells seem particularly easy to isolate and grow. The authors identified a set of cell-surface markers that allows the cells to be separated by flow cytometry from other cells in a tissue biopsy. And in vitro, the cells proliferated more quickly than either myogenic or endothelial cells did. They also resisted oxidative stress more effectively.

Although the researchers did not test whether myoendothelial cells could restore function directly, their potent muscle-regenerating capacity suggests that they have the potential to treat human muscle disease. Huard and Péault speculate that other multipotent adult stem cells could have the same lineage as myoendothelial cells. If so, the same protein signature should be able to identify multipotent stem cells in other adult tissues such as fat and skin.