Generation of expandable, self-renewing muscle stem cells for Duchenne Muscular Dystrophy

The goal of these studies is to define protocols to generate expandable, self-renewing human muscle stem cells from hiPS cells for Duchenne Muscular Dystrophy disease modeling and therapeutics. Although approaches to derive skeletal muscle cells from ES and iPS cells have been reported, they mainly give rise to committed progenitors, with limited self-renewal function. This major bottleneck prevents the use of DMD ES- and iPS-derived muscle progenitors for reliable disease modeling as well as cell replacement therapies. Our recent findings demonstrated that STAT3 signaling promotes the transition from MuSC to committed myogenic progenitors, and that pharmacological treatment with STAT3i promotes their expansion both in vitro and in vivo in DMD models. The results from this CIRM project provide evidence that STAT3 inhibition promotes the expansion of human iPSC-derived muscle stem cells in vitro. The integration of this strategy with current approaches to derive myogenic cells from hES and hiPS cells would facilitate the generation of muscle stem cells which are expandable in vitro. These studies will facilitate the generation of robust disease modeling platforms in vitro for muscle diseases and accelerate their translational towards clinical applications for regenerative medicine purposes.