Grants We Funded

Abstract
Muscle degenerative conditions affect millions in the United States, and diseases that target isolated small muscles and traumatic injuries to individual nerves or muscles disable over 1 million. Satellite cells, a population of resident stem cells in skeletal muscle, can proliferate and repair damaged muscle, making them promising targets for muscle regenerative therapies. Mouse satellite cells (MuSCs) have been transplanted and shown to correct histopathology and improve muscle function in disease models. Our laboratory recently isolated human skeletal muscle stem cells (hMuSCs) that regenerate skeletal muscle after transplant into a mouse, making them a potential source of regeneration-capable cells. Previous studies have reported that the number of satellite cells in denervate muscle decreases by approximately one-third after seven months; others have found that the inability of skeletal muscle to regenerate after prolonged denervation may be due to various factors, including physical barriers arising as a result of anatomic changes. However, it is not known whether muscle satellite cells in denervated muscle retain their stem cell characteristics. Determining whether the native muscle stem cell population in denervated muscle possesses regenerative potential, or whether supplementation of regeneration-capable cells from another source is necessary and feasible, will clarify what the most effective treatment strategies will be. The goal of this project is to determine a) whether intrinsic MuSC function and characteristics are maintained after denervation via flow cytometry and immunohistochemical techniques, b) the ability of hMuSCs to repopulate denervated muscle via transplantation and immunohistochemistry, and c) how hMuSCs affect histopathology and function of denervated muscle after reinnervation via immunohistochemistry and myo-mechanical analysis. This project will define whether muscle atrophy and dysfunction following denervation is, in fact, a disease affecting satellite cells, and whether their supplementation can improve muscle function in a model of peripheral nerve reinnervation following chronic denervation. If successful, a novel method of muscle regeneration will be available to those afflicted by chronic skeletal muscle denervation injury that may improve their functional outcomes after reinnervation, giving hope to patients with this unmet clinical need.

Biography
Alvin Wong, M.D. is a plastic surgery resident at UCSF and is currently a surgical research fellow in the Pomerantz Lab. Originally from New York, Dr. Wong received his A.B. in Biochemistry from Harvard College in 2007. He received his M.D. from Columbia University in 2012. In medical school he spent a year studying the effect of propranolol on hemangioma stem cells in the laboratory of Dr. June Wu, winning multiple awards for his research. He has completed three years of general surgical residency at UCSF, and with Dr. Jason Pomerantz is working on translational and basic science research projects studying the effect of nerve injury on muscle satellite cells. He plans to apply for a craniofacial fellowship when he has completed his plastic surgery training.