Human Adipose-Derived CD146(+) Stem Cells Increase Life Span of a Muscular Dystrophy Mouse Model More Efficiently than Mesenchymal Stromal Cells

摘要

Duchenne muscular dystrophy is the most common and severe form of progressive muscular dystrophy. Previous results showed an increased survival in double knockout mice (dko) when treated with adipose-derived CD146(+) cells. In this study, we analyzed the effect of CD146(+) cells compared to mesenchymal stem/stromal cells (MSCs) derived from the same human adipose sample when injected in the dko mouse model without immunosuppression. Both CD146(+) cells and MSCs increased the survival of treated mice when compared to vehicle-injected mice, with a more prominent effect of CD146(+) cells than MSCs. Both CD146(+) cells and MSCs suppressed peripheral blood mononuclear cell proliferation, indicating immunomodulatory properties. Co-culture experiments showed that MSCs have a more inflammatory profile expression, and angiogenesis assay showed that CD146(+) cells can improve blood vessel formation. CD146(+) cells can extend survival of muscular dystrophy mice more efficiently than MSCs, possibly due to immunomodulatory and angiogenic properties. Further investigations focusing on exogenous CD146(+) cell role in vivo will improve cell therapy understanding and effectiveness.