DEVELOPMENT OF BIOARTIFICIAL ENDOCRINE PANCREAS USING GLUCOSE-RESPONSIVE B-CELL LINE MIN6

使用葡萄糖反应性 B 细胞系 MIN6 开发生物人工内分泌胰腺

• 批准号: 07558247
• 负责人: MIYAZAKI Jun-ichi
• 金额: $ 2.05万
• 依托单位: Osaka University (1996)Tohoku University (1995)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558247/
• 关键词: diabetes; bioartificial endocrine pancreas; glucose transporter; MIN6 cell; insulin secretion; グルコーストランスポーター; バイオ人工膵島; インスリン

Embedded culture of pancreatic b-cells derived from a transgenic insulinoma (MIN6 cells) was studied in vitro and in vivo. The MIN6 cells were enmeshed in an agarose-PVMA-collagen matrix for long-term maintenance. The cells formed islet-like cell clusters (ICCs) in the mixed matrix. MIN6 cells exhibited normal b-cell function for up to 35 days in the matrix, and the cells were much better preserved with nicotinamide than without it. MIN6 cells were suspended in the matrix and transferred into diffusion chambers to create a bio-artificial endocrine pancreas (Bio-AEP). In streptozotocine-induced diabetic rats with implanted Bio-AEP but without any immunosuppressants, a return to normoglycemia was observed for up to 50 weeks after transplantation. Our results indicate that Bio-AEP containing MIN6 cells should be useful for the study of xenotransplantation and the development of a bioartificial endocrine pancreas, and opens a new field in the therapy of insulin-dependent diabetes mellitus.

对源自转基因胰岛素瘤（MIN6 细胞）的胰腺 b 细胞的包埋培养进行了体外和体内研究。将 MIN6 细胞浸入琼脂糖-PVMA-胶原蛋白基质中以进行长期维持。细胞在混合基质中形成胰岛样细胞簇（ICC）。 MIN6 细胞在基质中表现出正常的 b 细胞功能长达 35 天，并且使用烟酰胺的细胞比不使用烟酰胺的细胞保存得更好。将 MIN6 细胞悬浮在基质中并转移到扩散室中以创建生物人工内分泌胰腺 (Bio-AEP)。在植入 Bio-AEP 但未使用任何免疫抑制剂的链脲佐菌素诱导的糖尿病大鼠中，在移植后长达 50 周内观察到血糖恢复正常。我们的结果表明，含有 MIN6 细胞的 Bio-AEP 应可用于异种移植的研究和生物人工内分泌胰腺的开发，并为胰岛素依赖型糖尿病的治疗开辟了一个新领域。

项目成果

T.Kayo, et al.: "Proprotein-processing endoprotease furin decreases regulated secretory pathway-specific proteins in the pancreatic b-cell line MIN6." J.Biol.Chem.271. 10731-10737 (1996)

T.Kayo 等人：“前蛋白加工内切蛋白酶弗林蛋白酶可减少胰腺 b 细胞系 MIN6 中受调节的分泌途径特异性蛋白。”

Kayo,T.et al.: "Proprotein-processing endoprotease furin decreases regulated secretory pathway-specific proteins in the pancreatic β-cell line MIN6" J.Biol.Chem.271. 10731-10737 (1996)

Kayo, T. 等人：“前蛋白加工内切蛋白酶弗林蛋白酶减少胰腺 β 细胞系 MIN6 中受调节的分泌途径特异性蛋白质”J.Biol.Chem.271 (1996)。

Inada,S.et al.: "Rectification of diabetic state in C57BL/KsJ-db/db mice by the implantation of pancreatic beta cell line MIN6" Diab.Res.Clin.Pract.32. 125-133 (1996)

Inada,S.et al.：“通过植入胰腺 β 细胞系 MIN6 纠正 C57BL/KsJ-db/db 小鼠的糖尿病状态”Diab.Res.Clin.Pract.32。

Hagiwara, S. et al.: "An inhibitory role for phosphatidylinositol 3-kinase in insulin secretion from pancreatic b cell line MIN6." Biochem. Biophys. Res. Commun.214. 51-59 (1995)

Hagiwara, S. 等人：“磷脂酰肌醇 3-激酶对胰腺 b 细胞系 MIN6 分泌胰岛素的抑制作用。”

Wang, J.et al.: "Efficacy of microencapsulation of pancreatic B cell line (MIN6) in an agarose/PSSa microbead as a bioartificial pancreas." Transpl.Proc.28. 1094-1096 (1996)

Wang, J. 等人：“琼脂糖/PSSa 微珠中胰腺 B 细胞系 (MIN6) 微胶囊化作为生物人工胰腺的功效。”