Research Fellow Alvin Wong, M.D. Awarded Grant to Study Skeletal Muscle Regeneration
Alvin Wong, M.D., a plastic surgery research fellow in the Pomerantz Lab, was awarded a grant by the Plastic Surgery Foundation (PSF) to study "skeletal muscle regeneration by human satellite cells following denervation". The award, funded by a National Endowment for Plastic Surgery Grant, was one of eleven representing the "newest, clinically relevant research in plastic surgery".
The grant to Dr. Wong is also notable in that most such awards go to established principal Investigators with faculty appointments, a testament to the unique quality and scientific promise of the underlying research. Dr. Wong is mentored by Jason H. Pomerantz, M.D., Associate Professor of Surgery and Surgical Director of the UCSF Craniofacial Center.
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.
About the Pomerantz Lab
Led by Jason H. Pomerantz, M.D., Associate Professor of Surgery and Surgical Director of the UCSF Craniofacial Center, the Pomerantz Lab studies basic and translational aspects of tissue regeneration. With foundations in muscle and cancer biology, the lab investigates regenerative mechanisms including stem cell development and de-differentiation. Using model organisms such as zebrafish and mice, and extending discoveries to human cells and tissues, the lab hopes to gain fundamental insight that can be translated into clinical advances, notably solving the structural and reconstructive problems of the limbs, face, and head, whether congenital or acquired.