Discovery suggests bone marrow cells can travel to diseased muscle fibers

Children’s researchers have found that cells from a bone marrow transplant given to a 1-year-old boy remained in the his muscle tissue 13 years later. The findings suggest that human bone marrow cells can become part of diseased muscle fibers and and raise hopes for a future muscular dystrophy treatment.

The results, reported in September’s Journal of Clinical Investigation, come from a patient who suffers from two serious genetic diseases.

When the patient was 6 months old, doctors at Children’s Hospital Los Angeles diagnosed him with a severe immune deficiency resulting from a genetic mutation. He received bone marrow transplanted from his father to bolster his immune system. As the boy grew, he had problems walking and running, and when he was 12 physicians diagnosed him with Duchenne muscular dystrophy (DMD), a genetic disorder that affects about one in 4,000 males.

DMD shows up as general weakening of the muscles, starting in the limbs and the trunk. Most patients lose their ability to walk by the age of 10, and few survive beyond their twenties because weakening muscle fibers of vital organs such as the lungs cause fatal pneumonia or other complications.

But the Los Angeles patient’s DMD was intriguingly mild. Speculating that the transplanted bone marrow may have reduced the severity of the muscular dystrophy by producing healthy muscle cells, the patient’s Los Angeles doctors contacted Louis Kunkel, PhD, chief of Children’s Division of Genetics. Over the past five years, Kunkel and his Boston colleagues have shown that in mice, stem cells from transplanted bone marrow can restore the function of the dystrophin gene in individuals with DMD.

The Los Angeles patient offered unexpected evidence that the same effect may occur in humans with DMD. “It’s a beautiful experiment of nature,” Kunkel said.

The evidence, however, was far from conclusive. Researchers could not be sure that the bone marrow transplant lessened the symptoms of the disease or that the transplanted cells were the reason for the mild nature of the boy’s disease. To answer these questions, Emanuela Gussoni, PhD, first author of the paper and a geneticist at Children’s, examined the boys muscle tissue and found that the muscles did indeed contain a small number of the donated cells.

Disappointingly, subsequent analysis showed that those cells did not appear to have any effect on the severity of the boy’s DMD. However, the discovery of the donated cells in the patient’s muscle tissue 13 years after the transplant indicated that patients with DMD may benefit from bone marrow transplantation.

“It would have been nice to see whether the transplanted muscle cells were growing throughout those years,” says Gussoni. “It could be that the cells decreased or increased over time. However, the fact that the patient still has his father’s stem cells after 13 years indicates that the patient may be continuing to make muscle cells from the original transplant.”

To continue this research, researchers plan to give the boy a second bone marrow transplant from his father later this year, introducing more donated stem cells than in the first transplant. Only time will tell whether the therapy proves effective.

“If further research proves out,” Kunkel says, “it could help patients with any form of muscular disease — even someone who had muscle tissue damaged in an accident.”—CM

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