Cultured neonatal islet transplants in alloxan-treated and spontaneously diabetic rats

Neonatal Fischer-344 (FSH) islets isolated by a nonenzymatic method have been shown to survive indefinitely in Wistar/Furth (WF) recipients. We have applied this islet isolation method to six different donor strains and transplanted the resulting islets across 20 different strain combinations. We report the variable results obtained, with FSH being the most consistently successful donor strain and ACI being the best recipient strain. Based on the complete success of culture-derived FSH (Rt1lv1) and BN (Rt1n) transplants to WF (Rt1u) recipients, we used this system to test the MHC-restriction of autoimmune beta cell destruction in the BB/Wor rat (Rt1u). Culture-derived FSH and/or WF islets were transplanted to pre-diabetic BB/Wor recipients. Animals were sacrificed at the onset of disease or up to 33 days after disease onset. No immune response developed in FSH and WF grafts in non-diabetic animals. In diabetic animals, all FSH grafts and 12/14 WF grafts survived intact, although some grafts exhibited mild-moderate infiltration which was more pronounced in MHC-matched grafts. In two animals which developed severe hyperglycemia and ketosis, the FSH grafts were found to be intact while the WF grafts were destroyed by disease recurrence. In addition, FSH and BN islets were transplanted to diabetic BB/Wor recipients. Three of four FSH islet recipients and two of four BN islet recipients were reversed of their disease. Neither these nor the non-reversed animals showed signs of disease recurrence in the MHC-mismatched grafts. Therefore, in these studies, MHC-mismatched cultured grafts survived well and were capable of reversing the diabetic syndrome in spontaneously diabetic BB/Wor recipients.