Bioartificial pancreas transplantation for Type 1 diabetes

生物人工胰腺移植治疗 1 型糖尿病

• 批准号: 14571153
• 负责人: HISANAGA Michiyoshi
• 金额: $ 1.86万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571153/
• 关键词: Type-1 diabetes; Pancreatic islet transplantation; Agarose microcapsulation; Bioartificial Pancreas; Autoimmune reaction

[Aim] The recurrence of autoimmunity and allograft rejection act as major barriers to the widespread use of islet transplantation as a cure for type 1 diabetes. The aim of this study was to evaluate the feasibility of immunoisolation by use of an agarose microcapsule to prevent autoimmune recurrence after islet transplantation.[Methods] Highly purified islets were isolated from 6 to 8-week-old prediabetic male nonobese diabetic (NOD) mice and microencapsulated in 5% agarose hydrogel as a semipermiable membrane. Islet function was evaluated by a syngeneic islet transplantation model, in which islets were transplanted into spontaneously diabetic NOD mice.[Results] The nonencapsulated islet grafts were destroyed and diabetes recurred within 2 weeks after transplantation in all 12 mice. In contrast, 13 of 16 mice that underwent transplantation with microencapsulated islets maintained normoglycemia for more than 100 days after islet transplantation. Histologic examination of the nonencapsulated islet grafts showed massive mononuclear cellular infiltration with β-cell destruction. In contrast, the microencapsulated islets showed well-granulated β-cells with no mononuclear cellular infiltration around the microcapsules or in the accompanying blood capillaries between the microcapsules.[Condusions] Agarose microcapsules were able to completely protect NOD islet isografts from autoimmune destruction in the syngeneic islet transplantation model.

[目的]自身免疫复发和同种异体排斥反应是胰岛移植广泛应用于1型糖尿病治疗的主要障碍。为探讨应用琼脂糖微胶囊免疫隔离预防胰岛移植后自身免疫复发的可行性。[方法]从6~8周龄糖尿病前期雄性非肥胖糖尿病(NOD)小鼠分离高纯度胰岛，用5%琼脂糖水凝胶包埋成半透膜。用同种异体胰岛移植模型评价胰岛功能。[结果]12只小鼠移植后2周内无包膜胰岛均被破坏，糖尿病复发。相比之下，接受微囊化胰岛移植的16只小鼠中，有13只在胰岛移植后保持正常血糖超过100天。无囊化胰岛移植物的组织学检查显示大量单核细胞浸润并伴有β细胞破坏。相反，微囊化的胰岛显示颗粒完整的β细胞，微囊周围或微囊之间伴行的毛细血管内无单核细胞浸润。[结论]琼脂糖微胶囊能完全保护NOD胰岛移植物免受自身免疫破坏。

项目成果

Kobayashi T 他8名: "Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression."Transplantation. 75. 619-625 (2003)

Kobayashi T 和其他 8 人：“通过无免疫抑制的琼脂糖微胶囊对非肥胖糖尿病小鼠进行无限期的胰岛保护，使其免受自身免疫破坏。”移植。

T.KOBAYASHI, Y.Aomatsu, H.Iwata, T.Kin, H.Kanehiro, M.Hisanaga et al.: "Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression"Transplantation. 75・5. 619-625 (2003)

T.KOBAYASHI、Y.Aomatsu、H.Iwata、T.Kin、H.Kanehiro、M.Hisanaga 等人：“无免疫抑制的琼脂糖微囊化对非肥胖糖尿病小鼠的自身免疫破坏的无限期保护”75・5。 619-625 (2003)