title: Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.
abstract: 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.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: V
authors.initials: V
authors.lastname: Pathiraja
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: V
authors.initials: V
authors.lastname: Villani
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Matar
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Duran-Struuck
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: S G
authors.initials: SG
authors.lastname: Moran
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: E S
authors.initials: ES
authors.lastname: Clayman
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Hanekamp
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: C A
authors.initials: CA
authors.lastname: Huang
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007515:Islets of Langerhans / Q000098:blood supply*; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D008253:Macaca mulatta; D008297:Male; D014184:Transplantation, Homologous
keywords: islet isolation; islet transplantation; kidney transplantation/nephrology; tolerance: chimerism; tolerance: experimental; translational research/science