Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.

Published

Journal Article

We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20-22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain <200 mg/dL, whereas after IK Tx, three animals required minimal doses of insulin (1-3 U/day) and one animal was insulin free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression.

Full Text

Duke Authors

Cited Authors

  • Pathiraja, V; Villani, V; Tasaki, M; Matar, AJ; Duran-Struuck, R; Yamada, R; Moran, SG; Clayman, ES; Hanekamp, J; Shimizu, A; Sachs, DH; Huang, CA; Yamada, K

Published Date

  • January 2017

Published In

Volume / Issue

  • 17 / 1

Start / End Page

  • 91 - 102

PubMed ID

  • 27376692

Pubmed Central ID

  • 27376692

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/ajt.13952

Language

  • eng