title: Survival of microencapsulated islets at 400 days posttransplantation in the omental pouch of NOD mice.
abstract: The long-term durability of agarose microencapsulated islets against autoimmunity was evaluated in NOD mice. Islets were isolated from 6-8-week-old prediabetic male NOD mice and microencapsulated in 5% agarose hydrogel. Microencapsulated or nonencapsulated islets were transplanted into the omental pouch of spontaneously diabetic NOD mice. Although the diabetic NOD mice that received nonencapsulated islets experienced a temporary reversal of their hyperglycemic condition, all 10 of these mice returned to hyperglycemia within 3 weeks. In contrast, 9 of 10 mice transplanted with microencapsulated islets maintained normoglycemia for more than 100 days. Islet grafts were removed at 100, 150, 200, 300, and 400 days posttransplantation. A prompt return to hyperglycemia was observed in the mice after graft removal, indicating that the encapsulated islet grafts were responsible for maintaining euglycemia. Histological examination revealed viable islets in the capsules at all time points of graft removal. In addition, beta-cells within the capsules remained well granulated as revealed by the immunohistochemical detection of insulin. No immune cells were detected inside the microcapsules and no morphological irregularities of the microcapsules were observed at any time point, suggesting that the microcapsules successfully protected the islets from cellular immunity. Sufficient vascularization was evident close to the microcapsules. Considerable numbers of islets showed central necrosis at 400 days posttransplantation, although the necrotic islets made up only a small percentage of the islet grafts. Islets with central necrosis also showed abundant insulin production throughout the entire islets, except for the necrotic part. These results demonstrate the long-term durability of agarose microcapsules against autoimmunity in a syngeneic islet transplantation model in NOD mice.
authors.affiliation: First Department of Surgery, Nara Medical University, Nara, 634-8522, Japan. tsunehirokobayashi@hotmail.com
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Aomatsu
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kin
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kanehiro
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Hisanga
authors.forename: Saiho
authors.initials: S
authors.lastname: Ko
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagao
authors.forename: George
authors.initials: G
authors.lastname: Harb
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods* / Q000502:physiology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009852:Omentum; D012685:Sepharose / Q000737:chemistry / Q000627:therapeutic use; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000464:Alginates; D012685:Sepharose