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Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.

V Pathiraja1, V Villani1, M Tasaki1

  • 1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|July 5, 2016
PubMed
Summary

This study combined islet-kidney transplantation with hematopoietic stem cell transplantation in nonhuman primates to induce tolerance. The approach shows promise for curing diabetes and end-stage renal disease without immunosuppression.

Keywords:
islet isolationislet transplantationkidney transplantation/nephrologytolerance: chimerismtolerance: experimentaltranslational research/science

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Area of Science:

  • Regenerative Medicine
  • Immunology
  • Transplantation Biology

Background:

  • Prevascularized composite islet-kidney (IK) grafts previously reversed hyperglycemia in diabetic animals.
  • Inducing immune tolerance is crucial for the clinical success of allogeneic islet transplantation.

Purpose of the Study:

  • To evaluate the efficacy of combining hematopoietic stem cell transplantation (HSC Tx) with allogeneic IK Tx to induce immune tolerance in nonhuman primates.
  • To assess the potential of this combined strategy to cure diabetes and end-stage renal disease without long-term immunosuppression.

Main Methods:

  • Rhesus monkeys received autologous HSC Tx followed by conditioning (TBI, T-cell depletion, cyclosporine).
  • Allogeneic composite islet-kidneys (IKs) were transplanted into diabetic recipients 20-208 days after HSC Tx.
  • Graft acceptance and insulin requirements were monitored post-transplantation.

Main Results:

  • All transplanted IKs were accepted without rejection.
  • Three out of four recipients required minimal insulin (1-3 U/day), and one became insulin-free.
  • The combined strategy demonstrated successful islet engraftment and glycemic control.

Conclusions:

  • This study provides proof-of-principle for a novel tolerance strategy combining IK and HSC transplantation.
  • This approach may offer a potential cure for type 1 diabetes and end-stage renal disease, eliminating the need for immunosuppression.