MACROENCAPSULATED ARTIFICIAL PANCREAS

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First, unpurified islet transplantation(U IT) experiments were performed to evaluate the effects of various anticoagulants i.e. heparin, antithrombin III (ATIII), gabexate mesilate (FOY<encircledR>) on portal vein pressure, recipient survival, and graft survival when unpurified islets are transplanted into the portal vein using the isograft model. Male Wistar rats (200-300g) were used as donors and recipients. Fifteen minutes after the start of injection of cells, the portal vein pressure was measured. Recipients were divided into four groups. Unpurified islet transplantation (UIT) was performed with 100 units of heparin (group 1, n=6), heparin and 200 units/kg of antithrombin III (ATIII) (group 2, n=6), or heparin and 10 mg/kg of gabexate mesilate (FOY<encircledR>) (group 3, n=6). In group 4, 100 units of heparin was injected into the portal vein without transplantation as control (n=5).Long-term normoglycemia was not achieved, but one of the recipients in ATIII group was normoglycemic for 10 days. Two of 6, one of 6, three of 6, and none of 5 recipients in each group died due to portal hypertension followed by small bowel necrosis. In group 3, the portal pressure after transplantation was significantly lower than that in group 1 and 2, but still higher than that in controls.Further experiments are necessary to achieve safe and effective islet transplantation.Second, the function of bio-artificial pancreas derived from polysulfone membrane were investigated in vitro by using rat pancreatic islets. We used a gradient separation technique newly developed by Field et al , in which albumin-coated (35%BSA) rat islets are isolated in Dextran. The islets yield were 700-800 per pancreas. The viability of islets were investigated by static incubation which an artificial pancreas was incubated in RPMI solution containing 300 mg/dI of glucose. The mean insulin secretion was 29 ng/ml.