Intrinsic Myogenic Potential of Skeletal Muscle-Derived Pericytes from Patients with Myotonic Dystrophy Type 1.

Pericytes are multipotent, vessel-associated progenitors that exhibit high proliferative capacity, can cross the blood-muscle barrier, and have the ability to home to muscle tissue and contribute to myogenesis. Consequently, pericyte-based therapies hold great promise for muscular dystrophies. A complex multi-system disorder exhibiting muscular dystrophy for which pericytes might be a valuable cell source is myotonic dystrophy type 1 (DM1). DM1 is caused by an unstable (CTG)n repeat in the DMPK gene and characterized by skeletal muscle weakness, muscle wasting, and myotonia. We have successfully isolated alkaline phosphatase-positive pericytes from skeletal muscle of DM1 patients and a transgenic mouse model. Intranuclear (CUG)n RNA foci, a pathogenic DM1 hallmark, were identified in human and mouse pericytes. Notably, pericytes from DM1 patients maintained similar growth parameters and innate myogenic characteristics in vitro compared to cells from unaffected controls. Our in vitro results thus demonstrate the potential of pericytes to ameliorate muscle features in DM1 in a therapeutic setting.