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New Stem Cell Process Could Yield Effective Muscular Dystrophy Treatment

Their work, published May 4 in Cell Stem Cell, sets the stage for future human clinical trials.

The research was led by Rita Perlingeiro, Ph.D., associate professor of medicine in the UM Medical School's Division of Cardiology. It outlines the development of a rapidly dividing population of skeletal myogenic progenitor cells (muscle-forming cells) derived from induced pluripotent (iPS) cells. The iPS cells were derived by reprogramming skin cells, so they can be patient-specific, which renders them unlikely to be rejected. They also do not involve embryos, so are free from that controversy.

In the study, the UM researchers genetically modified two well-characterized human iPS cell lines and an existing human embryonic stem cell (ES) line with the PAX7 gene. This allowed them to regulate levels of the Pax7 protein, which is essential for the regeneration of skeletal muscle tissue after damage. The researchers found this regulation could prompt naive ES and iPS cells to differentiate into muscle-forming cells.

Up until this point, researchers had struggled to efficiently make muscle from ES and iPS cells. PAX7 — induced at exactly the right time — helped determine the fate of the ES and iPS cells, pushing them into becoming human muscle progenitor cells.

Once Dr. Perlingeiro's team was able to pinpoint the optimal timing of differentiation, the cells were well suited to the regrowth needed to treat conditions such as muscular dystrophy. In fact, Pax7-induced muscle progenitors were far more effective than human myoblasts at improving muscle function. Myoblasts (cell cultures derived from adult muscle biopsies) had previously been tested in clinical trials for muscular dystrophy, but did not persist after transplantation.

"Seeing long-term maintenance of these cells without major adverse side effects is exciting," Dr. Perlingeiro said. "Our research proves that these differentiated stem cells have real staying power in the fight against muscular dystrophy."

The UM researchers are currently testing alternate methods for delivering the Pax7 before clinical trial as the method they used in the study involved genetic modification of cells with viruses, which sometimes leads to mutations.

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