Shannon Anderson

BME PhD Defense Presentation

Date: Wednesday, May 26, 2021

Time: 1:00 PM

Bluejeans Link: https://bluejeans.com/309998463

Committee Members:

Nick Willett, Ph.D. (Advisor)

Young Jang, Ph.D. (Advisor)

Johnna Temenoff, Ph.D.

Edward Botchwey, Ph.D.

Khalid Salaita, Ph.D.

Jarrod Call, Ph.D.

Title: Aberrant Cellular Response and Muscle Regeneration Following Volumetric Muscle Loss

Abstract: 

Skeletal muscle has robust regenerative capacity after minor injury. However, following the traumatic loss of a large portion of tissue, known as volumetric muscle loss (VML), the muscle is unable to recover and will have chronic functional deficits. VML injury results in the concurrent loss of extracellular matrix (ECM), muscle stem cells (MuSCs), and all support cells which typically direct muscle regeneration. The overall objective of this thesis was to characterize the aberrant cellular response which leads to the accumulation of non-functional fibrotic tissue following critically sized VML injury. We first defined the threshold of a critical VML, where myofibers no longer bridge the defect created in the mouse quadriceps. When compared to subcritical injuries, critical VML resulted in distinct immune infiltration dynamics and fibro-adipogenic progenitor cells (FAPs) which were persistently elevated and localized in the VML defect. Further, surface marker analysis revealed a subset of pro-fibrotic FAPs specific to critical VML which highly expressed β1-integrin. Initial analyses also indicated a potential anti-myogenic role for this FAPs subpopulation. We then transplanted structurally aligned, myoblast-seeded collagen scaffolds in critical VML. We found these cell-seeded scaffolds improved maximal isometric torque over time and promoted cell engraftment. Overall, this thesis has contributed a critical VML injury model with well-defined cellular and tissue pathology. Additionally, the identification of a novel subpopulation of pro-fibrotic FAPs specific to critical VML combined with our use of a versatile biomaterial scaffold for cell transplantation together provide the groundwork for the development of future targeted therapeutics for VML.