The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs

PLoS One. 2013 Aug 1;8(8):e70150. doi: 10.1371/journal.pone.0070150. Print 2013.

Abstract

Developing a device that protects xenogeneic islets to allow treatment and potentially cure of diabetes in large mammals has been a major challenge in the past decade. Using xenogeneic islets for transplantation is required in light of donor shortage and the large number of diabetic patients that qualify for islet transplantation. Until now, however, host immunoreactivity against the xenogeneic graft has been a major drawback for the use of porcine islets. Our study demonstrates the applicability of a novel immunoprotective membrane that allows successful xenotransplantation of rat islets in diabetic minipigs without immunosuppressive therapy. Rat pancreatic islets were encapsulated in highly purified alginate and integrated into a plastic macrochamber covered by a poly-membrane for subcutaneous transplantation. Diabetic Sinclair pigs were transplanted and followed for up to 90 days. We demonstrated a persistent graft function and restoration of normoglycemia without the need for immunosuppressive therapy. This concept could potentially offer an attractive strategy for a more widespread islet replacement therapy that would restore endogenous insulin secretion in diabetic patients without the need for immunosuppressive drugs and may even open up an avenue for safe utilization of xenogeneic islet donors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomass
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / surgery
  • Diffusion
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiopathology
  • Islets of Langerhans / surgery*
  • Islets of Langerhans Transplantation / immunology*
  • Islets of Langerhans Transplantation / instrumentation*
  • Male
  • Membranes, Artificial*
  • Oxygen / metabolism
  • Rats
  • Swine
  • Swine, Miniature*
  • Time Factors
  • Transplantation, Heterologous / instrumentation*

Substances

  • Membranes, Artificial
  • Oxygen

Grant support

This work was funded by Beta-O2 (http://www.beta-o2.com/), the Deutsche Forschungsgemeinschaft grants (http://www.dfg.de/en/) SFB TRR 127 “Biology of xenogeneic cell, tissue and organ transplantation” (to BL, SRB), BR 1179 (to BL), and KFO 252 (to BL, SRB), Dresden Centre of Excellence (http://ccoe-dresden.de/), Centre for Regenerative Therapies Dresden (http://www.crt-dresden.de/), Paul Langerhans Institute Dresden - The German Center for Diabetes Research (http://www.dzd-ev.de/en). The funders (except for Beta-O2) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Beta-O2 had a role in study design, data collection, and analysis.