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Tolerance of Vascularized Islet‐Kidney Transplants in Rhesus Monkeys
Author(s) -
Pathiraja V.,
Villani V.,
Tasaki M.,
Matar A. J.,
DuranStruuck R.,
Yamada R.,
Moran S. G.,
Clayman E. S.,
Hanekamp J.,
Shimizu A.,
Sachs D. H.,
Huang C. A.,
Yamada K.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13952
Subject(s) - renal capsule , medicine , islet , transplantation , immunosuppression , kidney , insulin , endocrinology , miniature swine
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. IK s 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 T x. HSC T x 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 T x was performed either 20–22 (n = 3) or 208 (n = 1) days after HSC T x. All animals accepted IK s without rejection. All recipients required >20 U/day insulin before IK T x to maintain <200 mg/ dL , whereas after IK T x, 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.