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Muscle stem cell identity confirmed by researchers (9/18/2008)
Tags:
muscles, stem cells, muscle stem cells

A single cell can repopulate damaged skeletal muscle in mice, say scientists at the Stanford University School of Medicine, who devised a way to track the cell's fate in living animals. The research is the first to confirm that so-called satellite cells encircling muscle fibers harbor an elusive muscle stem cell.

Identifying and isolating such a cell in humans would have profound therapeutic implications for disorders such as muscular dystrophy, injury and muscle wasting due to aging, disuse or disease.

"We were able to show at the single-cell level that these cells are true, multipotent stem cells," said Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology. "They fit the classic definition: they can both self-renew and give rise to specialized progeny." Blau is the senior author of the research, which will be published Sept. 17 in the online issue of Nature.

"We are thrilled with the results," said Alessandra Sacco, PhD, senior research scientist in Blau's laboratory and first author of the research. "It's been known that these satellite cells are crucial for the regeneration of muscle tissue, but this is the first demonstration of self-renewal of a single cell."

One-tenth of the body's mass is skeletal muscle. Satellite cells hang out between a muscle fiber and its thin, membrane-like sheath, waiting to spring into action when the fiber is damaged by exercise or trauma. When necessary, they begin to divide to make more specialized muscle cells. This property alone, however, doesn't qualify them as stem cells. That designation requires them to be able to also make copies of themselves for future use.

Although many researchers suspected that the satellite cell population included muscle stem cells, it was difficult to prove because not all satellite cells are identical. It was possible that one subpopulation was responsible for making lots of specialized muscle cells, while another replenished the supply of satellite cells.

This divide-and-conquer approach might be efficient, but doesn't have the same exciting clinical applications as identifying a true stem cell. However, analyzing the specific properties of a single cell is technically difficult, and usually requires hundreds of hours of painstaking microscopic analysis of tissue slices from many laboratory animals.

Sacco used a trick to overcome these hurdles. She isolated satellite cells from a mouse genetically engineered to express a glowing protein, luciferase, first identified in fireflies. She then used a novel imaging technique developed at Stanford to follow their fate after transplantation into living animals that did not express the protein. Because this non-invasive method allows repeated imaging of the same animal, fewer mice are needed for the research.

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