Synergistic effect of microencapsulation and immunoalteration on islet allograft survival in bioartificial pancreas

Recently, we reported successful transplantation (Tx) of microencapsulated (mc) islets. However, graft failure observed in several cases was associate d with an increased foreign body reaction compared to long-term functioning grafts. This study was performed to investigate the impact of an immunoalt erating islet pretreatment (12-14 days culture at 22 degrees C) on graft fu nction. After microencapsulation in barium alginate beads the islets were c ultured for another day. Diabetic LEWIS rats (blood glucose >19 mM) were tr ansplanted with 3500 immunoaltered mc-Wistar islets intraperitoneally. Cont rols were transplanted with 3500 non-cultured syngeneic or allogeneic mc-is lets. Additional syngeneic and allogeneic controls were transplanted with 6 000 non-cultured, non-encapsulated islets intraperitoneally. Seventy percen t of the recipients of microencapsulated, long-term low temperature culture d islets maintained normoglycemia at least for 15 weeks, while this was tru e in only 17% of those animals receiving microencapsulated non-pretreated a llogeneic islets. Islets in non-encapsulated controls were rejected within several days. Graft function correlated with histologically proven viable i slets within the capsules. Microencapsulation of islets markedly prolonged allograft survival compared to non-encapsulated islets; application of an i mmunoaltering low-temperature culture further improved graft function signi ficantly. These data may support the hypothesis of induction of a reaction against microcapsules by the antigen release from the graft which may be av oided by immunoaltering islet pretreatment.