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Scientists closer to identifying cells that could rebuild muscle

Experiments in mice pinpoint muscle-forming cells

BY AMY ADAMS

Medical school researchers, led by Irving Weissman, MD, have characterized two groups of cells in adult mice that can fuse with and repair muscle cells. The human counterparts of these cells could prove useful for repairing muscles damaged by disease or for studying how muscles develop.

One of the two groups of cells, known as a satellite cell, sits dormant in muscles, coming to life if the muscle is damaged. According to Weissman, the Karel and Avice Beekhuis Professor of Cancer Biology, the existence of these cells has been known for years, and they were thought to be one of a type of cells, known as adult stem cells, which exist in adult tissues and can form a variety of cells in that tissue. The new findings pin down which of the diverse population of satellite cells is the likely muscle-forming stem cell.

The second group of cells is carried by the blood to tissues throughout the body. These were first identified in a 2002 paper in Cell by Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology. While Weissman’s study validates Blau’s findings that this group of cells can fuse with muscle cells, it suggests that this transformation is rare.

If the muscle-forming subset of satellite cells prove to be the muscle stem cells, they will join blood- and brain-forming adult stem cells, which have shown promise in treating diseases of the blood and brain. Weissman said he also hopes that muscle stem cells may one day help to treat muscular dystrophy and other muscle diseases.

Still, Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences and coauthor on the paper, cautioned that identifying the muscle stem cell won’t solve the problem of enticing these cells to treat disease.

“What’s clear is that stem cells in general respond to their environment,” he said. “If they are in the wrong environment they won’t activate.” Injecting a muscle stem cell into a damaged muscle or into the bloodstream of a person with muscular dystrophy won’t be of any use if that stem cell doesn’t recognize the tissue’s cry for help.

By identifying both satellite cells and the rare blood-borne cells as contributing to muscle, Weissman and Rando’s study, published in the Nov. 12 issue of Cell, smoothes some previous controversy over which cells can form mature muscle.

In a review accompanying the paper, Terence Partridge, a professor at the MRC Clinical Science Centre in London, wrote that the findings “cuts a swathe through the main areas of altercation,” over which cell type primarily contributes to adult muscle—the satellite cell. However, Partridge noted that the cells from the blood could still have “therapeutic applicability.”

“What’s exciting is that they can contribute to muscle,” Blau said. “Now what we need to do is figure out how to enhance this phenomenon.”

Rando, for one, agreed that rarity doesn’t equal impossibility. “Rare events can have therapeutic potential, but there is a huge gap between imagining the potential and realizing it,” he said.

One benefit of finding blood cells that migrate to muscle is that injecting these cells into the bloodstream places them squarely in their natural habitat. “You’d love to be able to inject a therapeutic cell intravenously and somehow have them distribute themselves in a uniform physiologic manner,” Rando said.

Satellite cells are out of their normal environment in the bloodstream and so far haven’t been able to make their way to muscle tissue when injected in this manner.

Whichever cell type a researcher chooses to work with, Rando said the problem is in moving from studying the process to treating disease. “Understanding something is easier than getting it to do what you want,” he said. “It comes down to trying to get nature to behave.”