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Studies on Diffusion Chamber for Bio-artificaial Endocrine Pancreas

生物人工内分泌胰腺扩散室的研究

基本信息

批准号：
60480311
负责人：
SAKURAI Yasuhisa
金额：
$ 3.84万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

Bio-artificial endocrine pancreas (Bio-AEP) containing islet cells is more capable of curing the homeostasis of diabetic patients than mechamical insulin delivery system from the long term physiological viewpoint. Islet cells separated from mouse or rat pancreas were cultured in monolayer with 3 isobuty1-1-methylxanthine (IBMX) added to medium, so as to keep ptheir viability to secrete insulin and other hormons in response to glucose concentration for a long period. Monolayer cells cultured on plastic plate should be enclosed with semipermeable polymer membrane in order to block the passing of immunoglobulins and lymphocytes inducing the host's immune reaction. At the same time polymer membrane should pass such useful substances as glucose, insulin and albumin.An implantable diffusion chamber for Bio-AEP was developed, which consisted of a small size holder, a culture plate with monolater islet cells and polymer membranes envelopping culture plate. Bio-AEP using mouse or rat islet cells were implanted into intraperitoneal cavities of mice. In case of isograft (mouse to mouse) implantation, glucose metabolism of diabetic animal recovered to mormal state for 100 days. However, in case of xenograft islets (rat to mouse), hyperglycemia of diabetic animal was slightly relieved only for 60 days. The passage of immunological substances was suspected as the cause of insufficient function of exnograft. The semipermeable membrane envelopping culture cells is key point of diffusion chamber type Bio-AEP Synthetic nuclepore and fluoropore membrane (pore size 0.03 - 0.6 <mu>m, membrane thickness 10 - 50 <mu>m) and capsule membrane of rabbit kidney were examined on their pormability of insulin, albumin and <gamma>-globulin. The result of experiment indicated that nuclepore of 0.03 <mu>m pore size and capsule membrane of kidney were preferable to others. The further biocompatible membrane should be developed in the field of biomaterials' science.

含胰岛细胞的生物人工内分泌胰腺（Bio-artificial endocrine pancreas，Bio-AEP）从长期生理学角度看比机械胰岛素输送系统更能改善糖尿病患者的内环境稳定。从小鼠或大鼠胰腺分离的胰岛细胞在单层培养中加入3-异丁基-1-甲基黄嘌呤（IBMX），以保持其对葡萄糖浓度的反应性，从而使胰岛细胞能长期分泌胰岛素和其它胰岛素。单层细胞在塑料板上培养时，应采用半透性高分子膜封闭，以阻断免疫球蛋白和淋巴细胞的通过，从而诱导宿主的免疫反应。研制了一种用于Bio-AEP的可植入式扩散室，该扩散室由小型保持器、单层胰岛细胞培养板和覆盖培养板的高分子膜组成。将使用小鼠或大鼠胰岛细胞的Bio-AEP植入小鼠的腹腔内。在同种移植物（小鼠到小鼠）植入的情况下，糖尿病动物的葡萄糖代谢在100天内恢复到正常状态。然而，在异种移植胰岛的情况下（大鼠到小鼠），糖尿病动物的高血糖仅在60天内轻微缓解。免疫物质的通过被怀疑是移植物功能不全的原因。半透性膜分离培养细胞是Bio-AEP扩散室的关键。本文研究了合成核孔膜、荧光孔膜（孔径0.03 - 0.6 <mu>μ m，膜厚10 - 50 <mu>μ m）和兔肾包膜膜对胰岛素、白蛋白和<gamma>β-球蛋白的渗透性。实验结果表明，以0.03 μ m孔径的核孔<mu>和肾包膜为最佳。生物相容性膜是生物材料科学研究的一个重要领域。