Researchers at the Harvard Stem Cell Institute have demonstrated for the first time that transplanted muscle stem cells can restore healthy muscle and improve muscle function in mice with muscular dystrophy. The research is published in the July 11 issue of Cell.
The injected cells also replenished the pool of regenerative stem cells normally found in muscle. Those stem cells allowed the treated muscle to undergo subsequent rounds of injury repair, the researchers discovered; in some cases, the stem cells replaced more than 90 percent of the muscle fibers.
"Our work shows proof-of-concept that purified muscle stem cells can be used in therapy," said Amy Wagers of Harvard, who added that her team is now working on isolating stem cells equivalent to those in the mouse from human muscle.
The results of Wagers' research show that regenerative muscle stem cells can be identified among other muscle cells by unique protein markers on their surfaces. Using these markers, the researchers were able to select stem cells from normal adult muscle and transfer them to the diseased muscles of mice with a mutation in the same gene targeted by human Duchenne muscular dystrophy, for which there is no cure.
"Once the healthy stem cells were transplanted into the muscles of the mice with muscular dystrophy, they generated cells that incorporated into the diseased muscle and substantially improved the ability of the treated muscles to contract," Wagers said. "At the same time, the transplantation of the healthy stem cells replenished the formerly diseased stem cell pool, providing a reservoir of healthy stem cells that could be re-activated to repair the muscle again during a second injury."
The study is likely to lead to efforts to identify pathways that regulate the muscle stem cells, in order to determine whether their regenerative potential can be increased, perhaps through drug therapies or genomic approaches. The long-term goal is to replicate Wagers' findings in humans.
"This is still very basic science, but I think we're going to be able to move forward in a lot of directions," Wagers said. "It opens up many exciting avenues."