Nia Myrie

BME PhD Proposal Presentation

Date: 2023-05-04
Time: 9:00 - 11:00 am
Location / Meeting Link: Pettit Microelectronics Building Room 102A; https://gatech.zoom.us/j/2503560220?pwd=K1RkcjVhM3VxNHFJV0xPQkt6Y3g0Zz09

Committee Members:
Andrés J. García, Ph.D. (Advisor); Young C. Jang, Ph.D.; Edward Botchwey, Ph.D.; Stanislav Emelianov, Ph.D.; Foteini Mourkioti, Ph.D.


Title: Engineering a Synthetic Hydrogel for Muscle Stem Cell Delivery to Dystrophic Diaphragm

Abstract:
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by the absence of dystrophin protein, which serves as structural support between the muscle fiber membrane and extracellular matrix (ECM). Without it, muscles undergo cycles of degeneration and regeneration, leading to wasting and weakness. Overtime, DMD patients suffer from ambulatory disability and cardiorespiratory failure, the latter of which is a major contributor to premature death. Currently, there is no cure. Although glucocorticoid steroid treatment has lengthened patients’ life span, this treatment has many negative side effects with short- and long-term use including furthering muscle weakness and atrophy. Gene therapies face obstacles related to mutation specificity and immunogenicity. An alternative treatment strategy is to transplant muscle satellite cells (MuSCs) to a target muscle to repopulate the stem cell niche and restore dystrophin to the muscle fibers. This strategy takes advantage of muscle cells’ ability to fuse with existing muscle fibers, thus allowing dystrophin from donor cells to enter the fiber. MuSCs are typically delivered via injection; however, poor cell retention and survival upon transplantation ultimately leads to low cell engraftment and functionality. Delivering MuSCs to the diaphragm muscle poses additional challenges due to its morphology and deep-seated location. This project seeks to address these challenges by leveraging hydrogels as a vehicle for localized delivery. In Aim 1, I will engineer a peptide-functionalized synthetic hydrogel for localized MuSC delivery to dystrophic diaphragms. In Aim 2, I will assess the effects of delivering encapsulated MuSCs to dystrophic mice diaphragms by evaluating morphological and functional changes in the diaphragm. I hypothesize that these hydrogels will promote MuSC survival, proliferation, migration, and fusion for increased engraftment to host muscle, thus restoring dystrophin and improving diaphragm morphology and function. A successful outcome can contribute to future work furthering this platform as a therapy that extends and improves DMD patients’ quality of life.

Graduate Academic Office 

Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology & Emory University 

GradAO@bme.gatech.edu| 404-385-0124