Strategies for producing muscle stem cells

Muscular dystrophies are a group of chronic disorders characterized by progressive loss of muscle functions that unfortunately have no cure. Stem cell therapy emerges as a promising approach because it promotes healing by replacing diseased muscles with healthy muscles. Recently I have reported a robust teratoma method that can produce muscle stem cells at large quantities from pluripotent stem cells, allowing regeneration of healthy fibers and improvement of muscle functions. In this application, I propose a series of experiments that make use of this teratoma method to study how muscle stem cells develop and expand. My goal is to discover pathways that are fundamental to muscle stem cells development and to use this information to invent new protocols in producing repopulating muscle stem cells as therapeutics.

Year 1 Progress Report:

Muscular dystrophies are a group of chronic disorders characterized by progressive loss of muscle functions. Among them, Duchenne muscular dystrophy is the most common in Minnesota and in the US. An ideal treatment for Duchenne muscular dystrophy would be to replace damaged muscles with new healthy muscles. There are currently 2 promising approaches to achieve this goal: 1) by harnessing the regenerative power of endogenous muscle stem cells, and 2) by deriving muscle stem cells from pluripotent stem cells. Our research aims to advance both of these approaches. In our first year, we have used the state-of-the-art single-cell RNA-sequencing technology to decipher how muscle stem cells derive from pluripotent stem cells. We have also discovered factors that might enable expansion of endogenous muscle stem cells to a clinically relevant amount for potential cell therapy.