Angélica Torres
BME PhD Proposal Presentation

Date: 2024-12-17
Time: 12pm-2pm
Location / Meeting Link: Whitaker 1103 https://gatech.zoom.us/j/91422102210?pwd=ym1Tg8012XRciEReAbfhAbfbUX5Sl3.1

Committee Members:
Andrés García, PhD (Advisor) Rebecca Levit, MD James Markmann, MD, PhD Jeffrey Millman, PhD Ankur Singh, PhD


Title: Vascularizing Synthetic Hydrogels for Engraftment and Function Stem Cell-Derived Islets in Subcutaneous Space

Abstract:
Type 1 Diabetes (T1D) is a chronic, autoimmune disease that results in the irreversible destruction of beta cells. The insulin produced by the beta cells is responsible for the regulation of blood glucose levels and without it, the blood glucose levels become dangerously high and multiple long-term health complications can arise. The transplantation of allogeneic islets shows promise as a cure, but donor availability and long-term survival of the cells have prevented its success. Pluripotent stem cell-derived islets (SC islets) have emerged as an alternative cell source for implantations due to their scalability. Furthermore, the subcutaneous space is a clinically relevant transplant site that is minimally invasive compared to the intrahepatic site, but it has low vascularization. To address this limitation, hydrogels made from 4-armed maleimide-terminated polyethylene glycol (PEG-4MAL) are useful for controlled delivery of vasculogenic endothelial growth factor (VEGF). Changes in the polymer backbone and crosslinker modulate the mode/rate of degradation, VEGF release, and subsequent survival of SC islets. I propose to investigate the ability of a PEG-4MAL+VEGF hydrogel system to promote the engraftment, survival, and function of human SC islets in immunodeficient diabetic mice and in a more clinically relevant transplant model: non-human primates.