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Newfound Stem Cells May Lead to Regenerative Therapies for Damaged Muscles

The discovery of versatile stem cells in muscle tissue could help combat the progression of muscular dystrophy.
satellite stem cell division



COURTESY OF MICHAEL RUDNICKI
Canadian researchers have identified a previously unknown type of stem cell in muscles that may one day be targeted to treat muscular dystrophy, a debilitating degenerative disease that affects some 250,000 Americans.

"It basically is the discovery of a new type of stem cell—a satellite stem cell," says Michael Rudnicki, director of the Sprott Center for Stem Cell Research at the Ottawa Health Research Institute (OHRI). So-called satellite cells were previously believed to be involved exclusively in helping injured muscles repair themselves.

But Rudnicki and colleagues found that mouse muscles actually contain two different types of satellite cells—90 percent of which are preprogrammed to become muscle tissue and another 10 percent that are uncommitted and could conceivably become bone, fat or some yet to be determined cell type.

The researchers report in Cell that they tagged muscle stem cells in mice in an attempt to track the activation of the gene Myf5. The gene codes for a protein, which functions, according to Rudnicki, as the "first genetic entry point into the muscle lineage."

They found that the gene was active in the stem cells predestined to become muscle, but switched off in the other version. When the cells operating sans active Myf5 divided, one of the daughter cells contained an activated gene and the other had no Myf5 function. When Myf5-positive genes were inserted, they just went on to become muscle cells. On the other hand, cells with the inactive genes divided into both types of stem cells, helping to replenish the entire satellite cell reserve.

The new discovery could lead to new therapies for degenerative diseases like muscular dystrophy, which is characterized by progressive weakening of skeletal muscle tissue. "I think where the promise lies is in understanding the molecular control and pathways of the cells," Rudnicki says.

He notes that in Duchenne muscular dystrophy, the most prevalent form of the disorder, preliminary evidence suggests that the satellite stem cells are largely depleted over time, allowing muscle damage to spread instead of being mended as stem cells are used up without being replenished. He says that muscle damage could potentially be slowed or halted in patients if they were treated with biological entities that could target and turn Myf5 off in some muscle stem cells, creating in turn more satellite stem cells to repopulate the dwindling cell reservoir.

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