SUBJECT: Ph.D. Proposal Presentation
BY: Karen Martin
TIME: Tuesday, March 17, 2020, 2:30 p.m.
PLACE: IBB Building, 1128
TITLE: Biomaterial-directed mesenchymal stem cell immunomodulation for enhanced bone repair outcomes
COMMITTEE: Dr. Andrés García, Chair (ME, Georgia Tech)
Dr. Edward Botchwey (BME, Georgia Tech)
Dr. Esma Yolcu (Department of Immunology, University of Louisville)
Dr. Nick Willett (Department of Orthopedic Surgery, Emory University)
Dr. Levi Wood (ME, Georgia Tech)


The immunomodulatory and pro-regenerative functions of mesenchymal stem cells (MSC) make them an attractive cell source for use in regenerative medicine applications. However, clinical translation is hampered by poor control over MSC survival, localization, phenotype, and secretome upon transplantation in vivo, as well as an incomplete understanding of how therapeutically delivered MSC interact with the host immune system to promote positive wound healing outcomes. The objective of this project is to utilize hydrogel delivery vehicles to promote MSC survival and immunomodulation in vivo and to evaluate the immune responses to these hydrogel-MSC therapies in a bone repair environment. This will be achieved through two specific aims: (1) Integrin-specific hydrogels will be evaluated for their ability to promote MSC persistence and immunomodulatory functions upon injection in vivo in immunocompetent mouse models. As there are several known species differences between human and murine immune cells and MSC, biomaterial-directed MSC secretome production and immune cell interactions will be evaluated in both a murine model using murine MSC and a humanized mouse model using human MSC, allowing for direct comparisons between species. (2) The impact of hydrogel-delivered MSC on bone healing and immune cell recruitment and phenotype over time will be evaluated in a murine segmental bone defect model. Using a combination of mass cytometry and single cell RNA-sequencing, key immune cell subpopulations that drive positive biomaterial-delivered MSC-dependent bone repair outcomes will be identified. The results of this proposal will yield critical insights into MSC-immune cell interactions in vivo and identify a means of modulating these interactions through the use of biomaterial-based MSC delivery vehicles.