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

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Publication Year:
2025
Authors:
Russell G Rogers, Jack Antich, Mario Fournier, Ariel Omidfar, Lizbeth Sanchez, Juliet Alfaro, Jonah Zarrow, Nancy Manriquez, Alessandra Ciullo, Jackelyn Valle, Eduardo Marban
PubMed ID:
40118057
Funding Grants:
Public Summary:
Duchenne muscular dystrophy (DMD) is a serious disease that causes muscles to weaken over time, leading to early death. Researchers tested special heart-related cells called cardiosphere-derived cells (CDCs) and tiny particles they release (called extracellular vesicles or EVs) as treatments in mice with DMD. They found that giving these CDCs regularly, starting early, helped keep the muscles strong and working well for up to a year. The tiny particles (EVs) also helped at first, but their effect faded after six months because the mice’s immune system started attacking them. The CDC treatment reduced muscle scarring and helped muscles grow. This shows that early, ongoing treatment with these cells could slow down DMD and supports testing this approach in people who are newly diagnosed.
Scientific Abstract:
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.