title: Composite islet-kidneys from single baboon donors cure diabetes across fully allogenic barriers.
abstract: We have previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reverses diabetic hyperglycemia in miniature swine. In order to test the potential clinical applicability of this strategy, we have extended it to a fully allogeneic nonhuman primate model. IKs were prepared in baboons by isolating islets from 50% to 70% partial pancreatectomies and injecting them under the autologous renal capsule, allowing vascularization before allogeneic Tx. Baboons with diabetes induced by stereptozotocin or total pancreatectomy, received composite IKs (n = 3) or free islets under the renal capsule or intraportally (n = 3), across fully allogeneic barriers with an immunosuppressive regimen consisting of ATG followed by MMF and tacrolimus. FBS of two of IK recipients decreased immediately after Tx and no insulin therapy was required throughout the experimental period (225 and 301 days). In contrast, all recipients of allogeneic free islets showed unstable FBS levels and required insulin within 2 months. We conclude that in addition to maintaining creatinine in the normal range, fully allogeneic IKs from single primate donors can achieve glucose regulation without insulin therapy, while free islets do not. These results support the feasibility of composite allogeneic IK Tx as a potential cure for end-stage diabetic nephropathy.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA, USA. kaz.yamada@tbrc.mgh.harvard.edu
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Hirakata
authors.forename: V
authors.initials: V
authors.lastname: Tchipashvili
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Iwaki
authors.forename: A
authors.initials: A
authors.lastname: Griesemer
authors.forename: P
authors.initials: P
authors.lastname: Vallabhajosyula
authors.forename: S
authors.initials: S
authors.lastname: Moran
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006943:Hyperglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007515:Islets of Langerhans / Q000098:blood supply*; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D008297:Male; D010180:Pancreatectomy; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose