Bone marrow cells can build new muscle

Scientists may have found the source of Mighty Mouse's strength. They've discovered that mouse marrow, the soft tissue inside bone, harbors cells capable of forming new muscle. This finding suggests novel avenues to explore in treating muscular dystrophies and other muscle-wasting diseases.

 In the March 6 Science, Italian scientists describe the ability of marrow cells to journey to the site of a muscle injury, where they seem to help mend damaged tissue. "They are recruited from the marrow, travel through the blood, actively pass through the blood vessel barrier, and repair muscle," says study author Fulvio Mavilio of the H. San Raffaele-Telethon Institute for Gene Therapy in Milan.

 Bone marrow has long been known as a reservoir of hematopoietic stem cells, which develop into white and red blood cells. Indeed, that's why bone marrow transplants are used to reconstitute a person's immune system.

 In recent years, researchers have also gathered evidence that some marrow cells, grown in the laboratory under particular conditions, can form bone, cartilage, fat cells, and muscle, says Darwin J. Prockop of Allegheny University of the Health Sciences in Philadelphia.

 Yet there has been little proof that marrow cells actually pursue such career choices inside the body. Mavilio's evidence came serendipitously. In experiments unrelated to muscle research, a colleague injected bone marrow cells into muscle and noticed that they appeared to form new muscle.

 To examine this unexpected phenomenon further, the researchers used snake venom to destroy limb muscle. They then took bone marrow from mice engineered to include a gene that expresses a marker protein only in muscle cells. When they transplanted this marrow into the damaged muscles of the other mice, they found that some regenerated muscle tissue displayed the marker, indicating that the foreign marrow cells had developed into muscle.

 Mavilio and his colleagues also injected bone marrow into the bloodstream of mice with damaged muscles and later saw muscle cells with the marker protein at the site of regeneration.

 The damaged muscle tissue must somehow lay down a chemical trail that attracts the marrow-derived muscle precursors, suggests Mavilio. "We don't know what those signals are. We have no idea at all," he says.

 Noting that most new muscle develops from so-called satellite muscle cells near the injured tissue and thus does not carry the marker, Mavilio cautions that his group has not yet proved that the marrow cells contribute significantly to regeneration.

 Indeed, Eric P. Hoffman of the University of Pittsburgh School of Medicine told Science News that several years ago, he and his colleagues found that bone marrow transplants had no therapeutic effect on a mouse version of a muscular dystrophy.

 Nevertheless, Hoffman says this latest research should renew interest in whether marrow-derived cells are more effective in treating muscular diseases than transplants of myoblasts, or mature muscle cells. That controversial technique has been abandoned by most investigators.

"If we could identify the muscle stem cells -- a true population that lives, proliferates, and regenerates skeletal muscle -- that would be critical for developing transplants as a true form of therapy," says Hoffman. He notes that few of the transplanted myoblasts have survived for long in patients.

 Furthermore, while physicians inject myoblasts into muscles, they might be able to inject the marrow-derived muscle precursors into the bloodstream, which would carry them to the appropriate muscles, speculates Mavilio.

 He warns that scientists have yet to show that marrow-derived muscle precursors exist in people. "All of this could still be a biological curiosity," he says.