Long-term preservation of muscle function and structure by repeated administration of cardiosphere-derived cells in mdx mice.

Duchenne muscular dystrophy (DMD) is a progressive myodegenerative disease that leads to severe muscle weakness and premature death. Mouse cardiosphere-derived cells (mCDCs) and extracellular vesicles (EVs) secreted by human cardiosphere-deriveds (hCDC-EVs) are therapeutic to mice with advanced-stage DMD. Here, we investigated the long-term benefits of monthly dosing when initiated early. At the endpoint, exercise performance and skeletal muscle function were strikingly preserved in mdx mice that had received mCDCs, but not in vehicle control. In contrast, the beneficial effects of hCDC-EVs waned after 6 months, in parallel with the development of anti-hCDC-EV antibodies. Further investigation showed that mCDCs lowered fibrosis and initiated a myogenic response program in mdx skeletal muscle. Thus, early and sustained intervention with mCDCs prevents disease progression for up to 1 year in mdx mice. This discovery offers new insights into how cell therapy can be used to treat DMD and motivates clinical testing of CDCs beginning in newly diagnosed DMD.