Long-term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques

Robert W. Holdcraft, Melanie J. Graham, Melissa A. Bemrose, Lucas A. Mutch, Prithy C. Martis, Jody L Janecek, Richard D. Hall, Barry H. Smith, Lawrence S. Gazda

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue. The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.

Original languageEnglish (US)
Article numbere12747
JournalXenotransplantation
Volume29
Issue number3
DOIs
StatePublished - May 1 2022

Bibliographical note

Funding Information:
The authors thank our colleagues at The Rogosin Institute for their contributions to this work, especially the islet isolation team of Lisa Circle, Hollie Adkins and Eric Meyer. We gratefully acknowledge the excellent and expert care, husbandry, and training of our animals by the team at the University of Minnesota's PCRC. We are also grateful to our colleagues at Bob Evans Farms, Inc., for their continued support of this project, especially Eric Winkle, Bob Blankenship and Mike Townsley. We thank the University of Minnesota Comparative Pathology Shared Resource for performing histology and Tim O'Brien and Meghan Moore for pathological interpretations. We thank Henk‐Jan Schuurman for scientific advice. Finally, the authors are indebted to Metromedia Bio‐Science LLC for their long‐term financial support of this project.

Funding Information:
The authors thank our colleagues at The Rogosin Institute for their contributions to this work, especially the islet isolation team of Lisa Circle, Hollie Adkins and Eric Meyer. We gratefully acknowledge the excellent and expert care, husbandry, and training of our animals by the team at the University of Minnesota's PCRC. We are also grateful to our colleagues at Bob Evans Farms, Inc., for their continued support of this project, especially Eric Winkle, Bob Blankenship and Mike Townsley. We thank the University of Minnesota Comparative Pathology Shared Resource for performing histology and Tim O'Brien and Meghan Moore for pathological interpretations. We thank Henk-Jan Schuurman for scientific advice. Finally, the authors are indebted to Metromedia Bio-Science LLC for their long-term financial support of this project.

Publisher Copyright:
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

  • diabetes
  • encapsulation
  • porcine islets
  • xenotransplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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