A porcine islet-encapsulation device that enables long-term discordant xenotransplantation in immunocompetent diabetic mice

Cell Rep Methods. 2022 Dec 21;3(1):100370. doi: 10.1016/j.crmeth.2022.100370. eCollection 2023 Jan 23.

Abstract

Islet transplantation is an effective treatment for type 1 diabetes (T1D). However, a shortage of donors and the need for immunosuppressants are major issues. The ideal solution is to develop a source of insulin-secreting cells and an immunoprotective method. No bioartificial pancreas (BAP) devices currently meet all of the functions of long-term glycemic control, islet survival, immunoprotection, discordant xenotransplantation feasibility, and biocompatibility. We developed a device in which porcine islets were encapsulated in a highly stable and permeable hydrogel and a biocompatible immunoisolation membrane. Discordant xenotransplantation of the device into diabetic mice improved glycemic control for more than 200 days. Glycemic control was also improved in new diabetic mice "relay-transplanted" with the device after its retrieval. The easily retrieved devices exhibited almost no adhesion or fibrosis and showed sustained insulin secretion even after the two xenotransplantations. This device has the potential to be a useful BAP for T1D.

Keywords: alginate; encapsulation; glycemic control; immunoisolation membrane; porcine islet; type 1 diabetes; xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / surgery
  • Diabetes Mellitus, Type 1* / surgery
  • Islets of Langerhans Transplantation*
  • Mice
  • Pancreas
  • Swine
  • Transplantation, Heterologous