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Author Notes:

Alice A. Tomei, atomei@miami.edu

TDT contributed to the design of the experiments, drafted the manuscript, generated data, and analyzed data. AAS contributed to the design of the experiments and generated data. FD, JCR, and GCG generated data. SAS, CJW, NMZ, and PB contributed to the design of the experiments. AAT conceived the project, designed the research, and supervised the study. AAT and PB revised the draft manuscript. All authors contributed to writing and editing the final manuscript.

The authors would like to thank the DRI Small Animal and Translational Models Core for management of diabetic mice; and the DRI Histology and Analytical Imaging Core for assisting with histological processing of samples.

AAT and AAS are inventors of the IP used in the studies and licensed to Sernova. AAT and AAS have received payment from Sernova related to the IP and stand to gain royalties from commercialization of the IP. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Research Funding:

Funding was provided by the Diabetes Research Institute Foundation and the National Institutes of Health (Grant R01DK109929). This work was also supported by NIH grant R01S10OD023579-01 for the VS.120 Slide Scanner housed at the University of Miami Miller School of Medicine Analytical Imaging Core Facility.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biotechnology & Applied Microbiology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • alginate
  • polyethylene glycol
  • capsules
  • type 1 diabetes
  • encapsulation
  • transplantation
  • ALLOGRAFTS

Parallel Evaluation of Polyethylene Glycol Conformal Coating and Alginate Microencapsulation as Immunoisolation Strategies for Pancreatic Islet Transplantation

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Journal Title:

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

Volume:

Volume 10

Publisher:

, Pages 886483-886483

Type of Work:

Article | Final Publisher PDF

Abstract:

Pancreatic islet transplantation improves metabolic control and prevents complications in patients with brittle type 1 diabetes (T1D). However, chronic immunosuppression is required to prevent allograft rejection and recurrence of autoimmunity. Islet encapsulation may eliminate the need for immunosuppression. Here, we analyzed in parallel two microencapsulation platforms that provided long-term diabetes reversal in preclinical T1D models, alginate single and double capsules versus polyethylene glycol conformal coating, to identify benefits and weaknesses that could inform the design of future clinical trials with microencapsulated islets. We performed in vitro and in vivo functionality assays with human islets and analyzed the explanted grafts by immunofluorescence. We quantified the size of islets and capsules, measured capsule permeability, and used these data for in silico simulations of islet functionality in COMSOL Multiphysics. We demonstrated that insulin response to glucose stimulation is dependent on capsule size, and the presence of permselective materials augments delays in insulin secretion. Non-coated and conformally coated islets could be transplanted into the fat pad of diabetic mice, resulting in comparable functionality and metabolic control. Mac-2+ cells were found in conformally coated grafts, indicating possible host reactivity. Due to their larger volume, alginate capsules were transplanted in the peritoneal cavity. Despite achieving diabetes reversal, changes in islet composition were found in retrieved capsules, and recipient mice experienced hypoglycemia indicative of hyperinsulinemia induced by glucose retention in large capsules as the in silico model predicted. We concluded that minimal capsule size is critical for physiological insulin secretion, and anti-inflammatory modulation may be beneficial for small conformal capsules.

Copyright information:

© 2022 De Toni, Stock, Devaux, Gonzalez, Nunez, Rubanich, Safley, Weber, Ziebarth, Buchwald and Tomei.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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