In preparation for injecting the new solution into a mouse model, the team first injected cardiotoxin into the mouse’s leg. The effect inhibited the production of dystrophin, causing a weakening of the muscle–a condition resembling muscular dystrophy. Perlingeiro and her colleagues then injected the mouse with the muscle-cell solution. The team then took muscle biopsies and, after immuno-staining, found that, compared with mice that did not receive the solution, treated mice exhibited more dystrophin, indicating healthy muscle regeneration.
To confirm their results, the researchers ran both groups of mice on a treadmill; they found that the mice that received the solution outlasted the group that did not. Perlingeiro went a step further: after sacrificing both animal groups, she and her colleagues extracted every leg muscle, treated or untreated. They then placed each muscle in a bath and tested its strength by exposing it to an electrical impulse. The team found that the stronger contractions came from the muscles treated with the stem-cell-derived solution.
Perlingeiro says that the study’s results are encouraging, as she envisions one day providing stem-cell-based therapy for people with muscular dystrophy and other muscle-related diseases. However, there will have to be more follow-up studies before the technique can be applied to humans.
“I have a long to-do list,” says Perlingeiro. “We’d like to use the same technique on human embryonic stem cells.”
Recently, researchers were able to turn human skin cells into embryonic stem cells, a technique that bypasses the thorny issues currently surrounding use of embryonic stem cells. Perlingeiro says that combining this technique with her muscle-deriving method may one day yield effective, efficient treatment of diseases such as muscular dystrophy.
“If we can reprogram skin cells to become pluripotent, and use Pax-3 to make muscle, then we would be able to make cells from the patient, and we wouldn’t face ethical issues or problems of rejection,” says Perlingeiro.
Paul Muhlrad, a research program coordinator for the Muscular Dystrophy Association, says that the study’s results are a promising step toward effective treatment for muscle-related diseases. “These researchers present a nice proof of principle that embryonic stem cells can be turned into muscle-producing cells in the laboratory and used to deliver healthy muscle to people with Duchenne muscular dystrophy,” says Muhlrad. “Of course, these experiments were done with mice. We’ve yet to see whether they will work in humans, but this study offers us much hope.”