Studies on Diffusion Chamber for Bio-artificaial Endocrine Pancreas

从长期的生理角度来看，含有胰岛细胞的生物人工内分泌胰腺(Bio-AEP)比机械胰岛素给药系统更有能力治疗糖尿病患者的体内稳态。从小鼠和大鼠胰腺分离出的胰岛细胞在单层培养中加入3-异丁基-1-甲基黄嘌呤(IBMX)，以保持其长期分泌胰岛素和其他激素的能力。培养在塑料平板上的单层细胞应用半透聚合物膜包裹，以阻止免疫球蛋白和淋巴细胞通过诱导宿主的免疫反应。同时，聚合物膜需要通过葡萄糖、胰岛素和白蛋白等有用物质。研制了一种植入式Bio-AEP扩散池，它由一个小尺寸的支架、一个含有单层胰岛细胞的培养板和包裹着高分子膜的培养板组成。将小鼠或大鼠胰岛细胞的Bio-AEP植入小鼠的腹膜腔内。在同种异体移植(小鼠对小鼠)的情况下，糖尿病动物的糖代谢在100天内恢复到正常状态。然而，在异种胰岛移植(大鼠到小鼠)的情况下，糖尿病动物的高血糖仅在60天内略有缓解。免疫物质的通过被怀疑是移植物功能不全的原因。半透膜包被培养细胞是扩散室型Bio-AEP合成核孔和荧光膜(孔径0.03~0.6 mm，膜厚10~50 mm)和兔肾囊膜对胰岛素、白蛋白和球蛋白的透过性测定。实验结果表明，0.03微米大小的核孔和肾脏的囊膜较好。生物材料科学领域应进一步发展生物相容膜。

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.