A stem cell transplant that fixes defective muscle in mice could someday become a treatment for muscular dystrophy
It may one day be possible to use cell transplants to treat muscular dystrophy.
A new study used skeletal muscle stem cells to rebuild brawn in mice with faulty muscle-making genes, researchers report in the July 11 Cell. The technique could provide a promising treatment for disorders like Duchenne muscular dystrophy, the most common form of the muscle disease.
The results offer hope that one day skeletal muscle stem cells from healthy people could be grafted into those with muscle disorders, says Amy Wagers, coauthor of the paper and a stem cell biologist at Harvard University and the Joslin Diabetes Center in Boston. People with other kinds of muscle damage could benefit as well, she says. “There are a lot of situations where muscle is degenerating or damaged and you might want to boost its regenerative capacity.”
Unlike ordinary cells, which each serve a specific purpose in the muscle, skeletal muscle stem cells are generalists, able to transform into any of the types of cells that make muscles. Different organs have different pools of stem cells.
Some research has tried to use bone marrow cells to
regenerate organ cells for the liver, the heart and other organs. But the new
work shows that drawing stem cells from the same type of organ being repaired
is more effective. “The paper confirms the fundamental idea that we have stem
cells residing in adult organs, and those are the cells that we should focus
on,” says Irina Conboy, a bioengineer at the
People with Duchenne face progressive muscle weakness. Because of a genetic defect, their bodies don’t make a protein called dystrophin, which is essential for maintaining the structural integrity of muscle. Without it, muscle becomes damaged and wastes away. Wheelchair-bound by their early teens, Duchenne patients typically die soon after, when their heart and diaphragm muscles can no longer keep them breathing, Conboy says.
To determine which cell types in the mice could best rebuild muscle tissue, Wagers and colleagues extracted stem cells from a pool of cells known to play a role in muscle growth and repair. To identify the best muscle rebuilders, the group analyzed the receptors on the cell surfaces.
Next, the group implanted muscle stem cells from normal mice into mice lacking the gene to make dystrophin. The mice have the same genetic defect as that implicated in Duchenne muscular dystrophy, Conboy says.
Within a couple of weeks of the transplant, mice with the stem cell transplant had markedly improved muscle fibers.
“They show 94 percent recovery, which is great,” Conboy says. “The first step is to discover how to restore muscle in an animal model, and I think that was done very successfully.”
Cerletti, M., et al. 2008. Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles. Cell 134(July 11):37-47.