BME PhD Defense Announcement for Rachel A. Morrison (S. Harbin and J. Rickus, co-advisors)

Everyone is invited to attend the public presentation beginning at 10:00 am.

Title: Oligomeric collagen encapsulation design and mechanism of protection for β-cell replacement therapy

Date: April 18^th

Time: 10:00 am

Location: Hybrid - MJIS 2001 and Zoom

https://purdue-edu.zoom.us/j/94970591432?pwd=WmJMbjI1eDYyb08rTmora0N5K29SZz09

Meeting ID: 949 7059 1432
Passcode: 780258

Advisory Committee: Sherry L. Harbin, Co-Chair; Jenna L. Rickus, Co-Chair; Kinam Park; Raghavendra G. Mirmira; Robert V. Considine

Abstract:

Type 1 Diabetes Mellitus (T1D), a chronic disease affecting over 1.5 million Americans, is characterized by the autoimmune destruction of insulin-producing β-cells within pancreatic islets. Islet/β-cell replacement therapies, where replenishable β-cell sources are implanted within protective microenvironments, have the potential to provide a long-term solution for individuals with T1D by restoring glucose-sensitive, insulin release and overall glycemic control. However, most conventional encapsulation materials elicit an immune reaction, known as a foreign body response (FBR), which compromises β-cell health and function. In this dissertation, we designed and evaluated various formulations of a polymerizable collagen, namely type I oligomeric collagen (Oligomer), as encapsulation materials for minimally invasive, subcutaneous delivery of replacement β-cells. Preclinical validation in chemically-induced diabetic mice demonstrated rapid (within 24 hours) reversal of diabetes for beyond 90 days with no signs of rejection or FBR after subcutaneous delivery of both allogeneic and xenogeneic (rat) islets. To further define this uncommon mechanism of protection, the tissue response to Oligomer, in comparison to commercial synthetic and collagen-based materials, was evaluated following subcutaneous implantation within rats, a well-established biocompatibility model. Histological and transcriptomics analyses were used to define the immune response at both cellular and molecular levels. Interestingly, Oligomer showed minimal and transient activation of innate immune cells similar to the sham surgical control, with no evidence of foreign body giant cell formation, inflammatory-mediated bioresorption, or fibrosis. Overall, this work evaluates preclinical efficacy and demonstrates mechanistic understanding of immune tolerance for Oligomer materials for β-cell replacement therapy and other regenerative medicine applications.