Researchers Find New Type of
Stem Cell For Possible Treatment of MD

Researchers at several U.S. and Italian institutions say they’ve isolated from human skeletal muscle a new type of stem cell that they believe could be “ideal” for the treatment of muscular dystrophy, the Muscular Dystrophy Association announced today.

MDA-supported Giulio Cossu at the San Raffaele Scientific Institute in Milan, Italy, and Paolo Bianco of the San Raffaele Biomedical Science Park in Rome led the team, which published results online today in Nature Cell Biology.

“This is the next logical step in developing a human clinical trial for stem cells in muscle disease,” said Sharon Hesterlee, MDA vice president of Translational Research. “Although recent results with animal cells have been promising, you can’t think about human therapies until you have human cells in hand.”

The researchers have dubbed the new cells “pericyte-derived.” Unlike so-called satellite cells, which are located just outside muscle fibers and can form new muscle cells under certain circumstances, these pericyte-derived cells are located around small blood vessels in muscle tissue.

In November, Cossu and colleagues announced they had isolated another blood-vessel-associated stem cell, in dogs, that can also give rise to muscle. They used these cells, called “mesoangioblasts,” to successfully treat canine muscular dystrophy. They say the cells in today’s paper may be related to mesoangioblasts, but they’re not yet sure.

When pericyte-derived cells taken from healthy human muscle tissue were given to mice missing the dystrophin protein (the cause of human Duchenne muscular dystrophy) and also lacking an immune system, they showed a very high rate of maturation into muscle fibers.

They also improved the ability of these mice to grip a rotating rod and stay on a treadmill.

The pericyte-derived cells demonstrated that they could cross blood vessel walls into muscle tissue when injected into an artery, an important requirement if cells are to be delivered through the bloodstream in humans.

The investigators also took pericyte-derived cells from children with Duchenne muscular dystrophy and injected the cells with miniaturized dystrophin genes before giving them to dystrophin-deficient, immunodeficient mice. These mice showed a similar improvement in functional performance compared to untreated mice, as did the animals that received cells from people without muscular dystrophy.

Using a patient’s own muscle cells, altered to make a needed protein such as dystrophin, is probably preferable to using cells from a donor. Scientists believe using a patient’s own cells will be less likely to provoke an unwanted immune response. (The mice in these experiments lacked an immune system, so this question couldn’t be addressed.)

The mice that were given human cells from healthy people and from children with Duchenne dystrophy both made significant numbers of muscle fibers and produced significant amounts of human dystrophin.

“In conclusion,” the authors of today’s paper say, “we have shown that pericytes represent a second myogenic [muscle-producing] precursor, resident in adult human skeletal muscle, with similar myogenic potency to, but ... distinct from, satellite cells. Because of these features, pericyte-derived cells are an ideal cell population for future cell therapy of muscular dystrophy.”

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is the most prevalent childhood form of muscular dystrophy, affecting about one in every 3,500 boys worldwide. Symptoms usually begin between ages 3 and 5, with difficulty climbing stairs and running. Weakness progresses until nearly all voluntary muscles, as well as the heart and respiratory muscles, are affected. Few patients survive into their 30s.

About the Muscular Dystrophy Association

The Muscular Dystrophy Association (MDA), founded in 1950, is a voluntary health agency; a dedicated partnership between scientists and concerned citizens aimed at conquering neuromuscular diseases that affect more than a million Americans. For more information, visit www.mda.org.