Improved Muscles in MD Animal Model

The mice used in the study lacked dystrophin, the same protein that humans with the fatal wasting disease also are missing.

„We envision eventually developing a stem-cell therapy for humans with muscular dystrophy, if we are able to successfully combine this approach with the technology now available to make human embryonic stem cells from reprogrammed skin cells,“ Dr. Perlingeiro from UT Southwestern Medical Center said. „These cells can be transplanted into the muscle, and they cause muscle regeneration resulting in stronger contractility.“

The researchers focused on manipulating genes that are active in the very early stages as embryonic stem cells start to develop into more specialized cells. At first, they activated a gene called Pax3, which is involved in creating muscle cells, and then injected those cells into the animals‘ muscles. Those cells caused tumors containing many different types of cells, indicating that there were still residual undifferentiated embryonic stem cells in the cultures at the time of implantation.
The researchers then began using fluorescent dyes to sort cells depending on whether some surface markers were turned on while others were turned off. By analogy, it was as if they were dealing with a crowd of people and wanted to pull out only those with red hair, green scarves and blue coats, while those with red hair, green scarves and no coats would be disqualified.

The final selection of cells, containing only one type, was again injected into the animals‘ hind-limb muscles. After a month, the fluorescent dyes showed that the cells had deeply penetrated the muscle, an indication that they were growing and reproducing as desired, and many of the muscle fibers also contained dystrophin, the key protein lacking in muscular dystrophy. After three months, the mice had no signs of tumors.

Tests of isolated muscles showed that the treated muscles were significantly stronger than untreated mice lacking dystrophin, although not quite as strong as those of normal mice. The same was true for tests on coordination.; Source: UT Southwestern Medical Center