Studies on Diffusion Chamber for Bio-artificaial Endocrine Pancreas

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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.