The field of stem cell biology as it applies to regenerative medicine requires a detailed understanding of what controls stem cell function. Our primary interest, therapeutically, is to transplant highly potent muscle stem cells (MuSCs) into the muscles of patients with muscular dystrophies. This offers a hope for a potential treatment or even cure of these devastating disorders. One of the main challenges is that MuSCs exist almost exclusively in a dormant state called the “quiescent” state, and it is in this state that they hold the greatest potential to regenerate muscle. This poses a major hurdle for therapy since these cells are rare in the body. Thus, it would be ideal if they could be grown to large numbers in culture without losing any of the potency of the quiescent state. Our main goal is to understand what controls the quiescent state in a MuSC’s native environment, or its “niche”. To do this will be purify quiescent MuSCs from human muscle tissue and we study their molecular and functional properties, particularly those that regulate quiescence. In addition, we will create artificial MuSC niches in order to recapitulate, in culture, the key elements that maintain MuSC quiescence and regenerative potential in vivo. Ultimately, understanding the regulation of quiescence will be a major breakthrough in our goal to use MuSCs to treat muscular dystrophies.
A major benefit to California of our studies will be to bring hope to the tens of thousands of patients with muscular dystrophies living in the state and for whom there are minimal treatments and no cures for these diseases. Still, due to the growing field of regenerative medicine from the investment of the citizens of California in CIRM, this state has become the world leader in the development of stem cell therapeutics. Our research would contribute substantially to this enterprise. This is particularly important because, as of now, there is only a single clinical trial ongoing in the world to use stem cells to treat muscular dystrophies, and that is a very small trial (6 patients) based in Italy. Despite decades of research by hundreds of laboratories around the world, several hurdles remain to realize the therapeutic benefit that has been envisioned, and among those major hurdles are finding cells that are numerous and potent enough to be feasible vehicles for stem cell therapies. We and many others believe that muscle stem cells (MuSCs) are just those cells, but we have to discover how best to capitalize on the potential of these cells so that, upon transplantation, they can both regenerate entire muscles and replenish the endogenous MuSC population, something that has eluded researchers. This is the main goal of our research, and the successful completion would put California at the forefront of stem cell therapeutics for muscular dystrophies.