Agarose-microencapsulated Islet Xenotransplantation

Abstract

Pancreatic islets were microencapsulated in an agarose hydrogel as a semipermeable membrane to prevent their xenorejection. We evaluated this bioartificical pancreas in discordant xenografting with or without administration of 15-deoxyspergualin (DSG). A 5% agarose suspension containing purified canine islets was emulsified in paraffin oil and solidified by cooling in an ice-bath. Canine islets were xenotrasplanted intraperitoneally in to BALB/c mice and NOD mice rendered diabetic with streptozotocin (220mg/kg body weight ip) and cyclophosphamide (200 mg/kg body weight ip), respectively. Graft survivals in BALB/c mice (37±28 days) and NOD mice (31±21 days) with microencapsulation were significantly longer than those without microencapsulation used as controls. With the combination of DSG (2.5mg/ kg per day) and microencapsulation, the islet xenograft survival (76±24 days, 75±27 days) could be extended much longer and indefinite graft survival was observed in two of seven, respectively. Regardless of whether, were low doses of DSG adminisered or not, mouse anti-dog antibody titer levels of BALB/ c were elevated to more than 50% two and four weeks after xenotransplantion of microencapsulated islets; however, their plasma glucose levels remained normal. Antibody-mediated damage to microencapsulated islet could not be detected. Combined therapy by agarose-microencapsulation and administration of DSG might be a promising strategy for clinical application to prevent rejection in discordant islet xenotransplantation.