Prolongation of culture-isolated neonatal islet xenografts without immunosuppression

Xenogeneic transplantation of 300-400 neonatal rat islets (Fischer 344) to the kidney subcapsular site of streptozotocin-induced nonimmunosuppressed diabetic adult mice (C57BL/6ByJ) resulted in a return to normoglycemia in 87% of the recipients. Of the 13 successfully reversed recipients, 5 exhibited graft rejection (hyperglycemia of +250 mg/dl) within 2 weeks posttransplantation, and 2 mice had rejected their rat islets by 3 weeks. The 6 remaining recipients exhibited significantly prolonged survival of the cultured islets: 1 remained reversed until 4 weeks posttransplantation, 2 remained normoglycemic for 5 weeks, in 3 diabetes remained reversed for more than 7 weeks--in one of these animals the disease was reversed for 17 weeks. Transplanted islets were isolated from neonatal rat pancreas during a period in culture that varied from 8 to 17 days. Although morphological integrity of the endocrine cells was confirmed by ultrastructural study, nonendocrine cells were not identifiable within the islets after 8 days of culture. Xenografted islets examined morphologically prior to obtaining physiological evidence of rejection were associated with extensive peripheral lymphocytic accumulation. Modification of islet immunogenicity leading to prolonged xenograft survival may reflect the degree to which the in vitro environment permits the differential survival of endocrine cells while purging the islet of cells initiating the immune response.