title: Histopathological study of intrahepatic islets transplanted in the nonhuman primate model using edmonton protocol immunosuppression.
abstract: While islet cell transplantation is a promising way to restore insulin independence to patients with type I diabetes mellitus, a detailed histological analysis of the transplanted, intraportal islets has not yet been reported. Rhesus macaques underwent total pancreatectomy, then had allogeneic isolated islets infused into their portal vein, followed by daclizumab, tacrolimus, and sirolimus to prevent islet rejection. Islets were evenly distributed among the liver lobes. Liver sections from a primate given allogeneic islets 5 d earlier did not display any islet capillary formation, whereas intrahepatic islets transplanted 30 and 90 d before euthanasia showed an abundant capillary supply. Localized hepatocellular glycogenosis was observed surrounding the islets in a primate with functioning islets 7 months post transplant. Liver sections from a primate that rejected islets transplanted 2 months prior displayed only islet remnants with prominent local lymphohistiocytic inflammation and an occasional capillary. We conclude that islets develop an abundant vascular supply within 30 d following transplant and because capillaries persist even following rejection, that the vascular cells are likely from the recipient. While transplanted islets were not vascularized early post transplant, the primates remained insulin independent. The long-term consequence of islets in the liver, marked by the glycogenosis, remains unknown and warrants further study.
authors.affiliation: Transplantation and Autoimmunity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.forename: Steven
authors.initials: S
authors.lastname: Mog
authors.forename: Noelle
authors.initials: N
authors.lastname: Patterson
authors.forename: John
authors.initials: J
authors.lastname: Leconte
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002196:Capillaries / Q000473:pathology; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000473:pathology; D007074:Immunoglobulin G / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000098:blood supply / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000473:pathology / Q000601:surgery*; D008253:Macaca mulatta; D018919:Neovascularization, Physiologic; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D016042:Transplantation, Heterotopic
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D020123:Sirolimus; D016559:Tacrolimus