Utilizing Microporous Annealed Particle (MAP) Gel as an Immunomodulatory Carrier for Islet Delivery
1Department of Surgery, University of Virginia Health System, Charlottesville, VA, 2Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, VA
Meeting: 2022 American Transplant Congress
Abstract number: 1513
Keywords: Graft acceptance, Graft survival, Islets, Rejection
Topic: Basic Science » Basic Science » 05 - Translational Cellular Therapies: Islet and Stem Cell Transplantation
Session Name: Translational Cellular Therapies: Islet and Stem Cell Transplantation
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: To investigate if coating with MAP gel improves dissociated or whole islet transplantation outcome.
*Background: MAP gel platform technology is composed of hydrogel microspheres that are assembled in situ to form a solid scaffold with open pore geometry (pores >10μm). When implanted subcutaneously in mice, MAP gel displays a non-immunogenic quality characterized by limited CD11b+ immune cell presence, scaffold volume retention, and lack of fibrous encapsulation. MAP gel can be designed to assist in islet engraftment by improving angiogenesis and limiting the immune response.
*Methods: a) C57BL/6 mouse islets were mixed with MAP gel and cultured in 24 well plates at 37°C. Viability of islets was scored following Propidium Iodide-Fluorescein Diacetate (PI/FDA) staining, and Glucose-stimulated insulin secretion (GSIS) assay was performed on Day 1, 3, 5, and 7 post-culture. The experiment was performed thrice. b) Single cells obtained from 30 C57BL/6 mouse dissociated islets were mixed with MAP gel, and cultured in 24 well plates at 37°C. Viability of cells was scored after PI/FDA staining and GSIS assay performed 1, 24, 48, and 72 hours post-culture. c) 100 C57BL/6 mouse islets were dissociated into single cells using Trypsin, mixed with MAP gel, and transplanted into syngeneic diabetic recipients under the kidney capsule. Blood glucose (BG) was measured daily and normoglycemia was defined as BG <200 mg/dL.
*Results: Mouse islets coated with MAP gel as well as uncoated islets retained >95% viability, with the stimulation index (SI) of MAP gel protected islets 3.2, and that of uncoated islets 2.4. The viability of dissociated islets protected with MAP gel was 84% with a SI=8.5 at 72 hours post culture. Uncoated cells from dissociated islets were nearly dead with only 35% viability, and SI=0.38 at 72 hours post culture. Single cells obtained from the dissociation of 100 C57BL/6 mouse islets, and that were co-transplanted with MAP gel under the kidney capsule, permanently returned transplanted diabetic mice to normoglycemia, with BG<200 mg/dL within 18 days post-transplantation (n=6). Treatment efficacy continued 40 days post-transplantation. The average BG measured at Day 30 was 163±38.2 mg/dL. Recipient mice transplanted with cells from dissociated islets without MAP gel remained hyperglycemic (n=6/group).
*Conclusions: MAP gel has significant translational potential in promoting graft survival of dissociated islets, and possibly even of stem cell-derived beta cells.
To cite this abstract in AMA style:Ma M, Chhabra P, Roosa C, Griffin DR, Brayman KL. Utilizing Microporous Annealed Particle (MAP) Gel as an Immunomodulatory Carrier for Islet Delivery [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/utilizing-microporous-annealed-particle-map-gel-as-an-immunomodulatory-carrier-for-islet-delivery/. Accessed March 26, 2023.
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