Sorted Muscle Progenitor Cells Reverse Muscular Dystrophy in a Mouse Model

Dystrophin has the longest gene known to date, measuring 2.5 megabases (0.1% of the human genome). Its gene's locus is Xp21 and has 97 exons, produces an mRNA of 14.6 kilobases and a protein of over 3500 amino acid residues.
To stimulate dystrophin production in embryonic stem cells, the investigators activated the Pax3 gene, which functions in muscle progenitor cells. However, when these cells were injected into mouse muscle, they caused the formation of teratomas, tumors containing cells of many different types of tissue.

To avoid tumor formation, the investigators utilized a fluorescent cell sorting process to concentrate muscle progenitor cells while rejecting undifferentiated, tumorogenic cells. Results published in the January 20, 2008, online edition of the journal Nature Medicine revealed that after the sorted cells were injected into the mice, they deeply penetrated the muscle tissue forming new muscle fiber. Many of the new muscle fiber cells contained dystrophin. Furthermore, after three months, the mice showed no signs of tumors.

"The problem had been that embryonic stem cells make everything,” explained senior author Dr. Rita Perlingeiro, assistant professor of developmental and molecular biology at the University of Texas Southwestern Medical Center. "They make a great variety of cells. The trick is to pull out only the one type you want. Even if there are 10 undesirable cells, that is too many. 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. These cells can be transplanted into the muscle, and they cause muscle regeneration resulting in stronger contractility.”


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University of Texas Southwestern Medical Center