ASSESSMENT OF INSULIN-SECRETION IN-VITRO FROM MICROENCAPSULATED FETALPORCINE ISLET-LIKE CELL CLUSTERS AND RAT, MOUSE, AND HUMAN PANCREATIC-ISLETS

Background. The possibility of transplanting microencapsulated pancrea tic islets into patients with insulin-dependent diabetes mellitus, eit her as allografts or xenografts, has attracted great interest, A criti cal evaluation of the results obtained reveals that the success has be en very limited. The aim of the present study was to compare the in vi tro function of microencapsulated islets obtained from adult humans, a dult mice, adult rats, and fetal pigs. Methods, Human pancreatic islet s were isolated at beta-Cell Transplant in Brussels, Belgium, and sent to the Department of Medical Cell Biology, Uppsala University in Upps ala, Sweden. Rat and mouse pancreatic islets and fetal porcine islet-l ike cell clusters (ICC) were prepared in Uppsala. All groups of islets were subsequently sent to the Department of Biotechnology, Norwegian Institute of Biotechnology, University of Trondheim, Trondheim, Norway , After 1 day in tissue culture, the islets were microencapsulated in alginate then cultured and sent back to Uppsala the next day, After ei ther overnight culture (day 1) or 6 days of culture (day 6), the micro encapsulated islets were examined for their insulin content and insuli n release, Nonencapsulated islets from the same isolations were used a s controls. Results. The insulin content of rodent and human islets wa s not affected by microencapsulation, whereas porcine ICC showed a dim inished insulin content. Microencapsulated porcine ICC also had a mark ed reduction in their insulin secretion in response to stimulation wit h glucose or glucose + theophylline both on days 1 and 6 in tissue cul ture. Mouse islets showed a reduced insulin response at both time poin ts. Rat islets exhibited an inhibition of insulin secretion on day 1, but this had been restored by day 6. Human islets had well-preserved i nsulin secretion after both days 1 and 6. Microencapsulated human isle ts showed a normal morphology 3-4 weeks after intraperitoneal transpla ntation to nude mice. Conclusions. Pancreatic islets isolated from hum an, rat, and mouse donors show a glucose-stimulated insulin release in vitro after microencapsulation and repeated transports between labora tories. The insulin secretory capacity of microencapsulated human and rat islets was preserved best, whereas mouse islets and particularly f etal porcine ICC were impaired by microencapsulation.