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

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 1999, Vol.77 (1), p.193-198
• Main Authors: ZEKORN, T. D. C, HORCHER, A, SIEBERS, U, FEDERLIN, K, BRETZEL, R. G
• Format: Article
• Language: English
• Subjects: Alginates; Animals; Biological and medical sciences; Blood Glucose - metabolism; Capsules; Cells, Cultured; Cold Temperature; Diabetes Mellitus, Experimental - surgery; Glucose Tolerance Test; Graft Survival; Histocompatibility Antigens Class II - metabolism; Islets of Langerhans - immunology; Islets of Langerhans - physiology; Islets of Langerhans Transplantation; Male; Medical sciences; Miscellaneous; Pancreas, Artificial; Rats; Rats, Inbred Lew; Rats, Wistar; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Transplantation, Homologous
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s001090050335

Recently, we reported successful transplantation (Tx) of microencapsulated (mc) islets. However, graft failure observed in several cases was associated with an increased foreign body reaction compared to long-term functioning grafts. This study was performed to investigate the impact of an immunoalterating islet pretreatment (12-14 days culture at 22 degrees C) on graft function. After microencapsulation in barium alginate beads the islets were cultured for another day. Diabetic LEWIS rats (blood glucose >19 mM) were transplanted with 3500 immunoaltered mc-Wistar islets intraperitoneally. Controls were transplanted with 3500 non-cultured syngeneic or allogeneic mc-islets. Additional syngeneic and allogeneic controls were transplanted with 6000 non-cultured, non-encapsulated islets intraperitoneally. Seventy percent of the recipients of microencapsulated, long-term low temperature cultured islets maintained normoglycemia at least for 15 weeks, while this was true in only 17% of those animals receiving microencapsulated non-pretreated allogeneic islets. Islets in non-encapsulated controls were rejected within several days. Graft function correlated with histologically proven viable islets within the capsules. Microencapsulation of islets markedly prolonged allograft survival compared to non-encapsulated islets; application of an immunoaltering low-temperature culture further improved graft function significantly. These data may support the hypothesis of induction of a reaction against microcapsules by the antigen release from the graft which may be avoided by immunoaltering islet pretreatment.