Survival of Microencapsulated Islets at 400 Days Posttransplantation in the Omental Pouch of NOD Mice

Cell Transplantation

Brief Communication

Yukio Aomatsu¹  Yoshiyuki Nakajima²  Michiyoshi Hisanga²  Mitsuo Nagao²  Saiho Ko²  Hiromichi Kanehiro²  Tsunehiro Kobayashi³  Hiroo Iwata⁴  Tatsuya Kin⁵  George Harb⁵ 

[1] Department of Surgery, Matsubara Municipal Hospital, Osaka, 580-0044, Japan;First Department of Surgery, Nara Medical University, Nara, 634-8522, Japan;First Department of Surgery, Nara Medical University, Nara, 634-8522, Japan;Surgical-Medical Research Institute, University of Alberta, Edmonton, Alberta, T6G 2N8, Canada;Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606–8507, Japan;Surgical-Medical Research Institute, University of Alberta, Edmonton, Alberta, T6G 2N8, Canada;

关键词: Islet transplantation;    Autoimmunity;    Microencapsulation;    Agarose;   

DOI  :  10.3727/000000006783981954

 received in 2005-02-14, accepted in 2005-10-11,  发布年份 2006

来源: Sage Journals

【 摘 要 】

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, β-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.

【 授权许可】

Unknown   
© 2006 Cognizant Comm. Corp.