Allotransplantation of Dispersed Single Pancreatic Endocrine Cells in Diabetic Rats

Abstract

Dispersed pancreatic endocrine cells (PECs) were recently shown to survive indefinitely in the brain of allogeneic diabetic rat recipients across the major histocompatibility barrier without immunosuppression. Purified PECs (2−3 × 106 cells) prepared from Wistar rat islets were transplanted in 10 different sites in streptozocin-induced diabetic ACI rats. Blood glucose and body weight changes were monitored throughout the study. PEC isografts (n = 5) and allografts (n = 6) were nonfunctional when transplanted in intramuscular, intravenous, and intrahepatic sites. When transplanted intraportally (n = 6) and intraperitoneally (n = 6), similar grafts were functional but had a short survival period (6.6 ± 1.5 and 15.3 ± 16.6 days, respectively). Prolonged graft survival in some recipients was observed when kidney capsule [5, 9, 10, 240, 282, and 300 (2 rats) days], omentum pocket (7, 8, 10, 90, 105, 154, 155, and 157 days), and testis (7, 8, 12, 150, 230, and 234 days) were the transplantation sites. Permanent graft survival was achieved in 20 of 20 recipients with intracerebral transplantation and 21 of 22 recipients with intrathecal transplantation. These findings confirm that dispersed single PECs can be transplanted as a permanent functional graft and can normalize the hyperglycemia of the diabetic recipients. The duration of PEC graft survival is variable and depends on the transplantation site. Both the cerebral cortex and subarachnoid space, which are immunologically privileged sites, have provided the best allograft protection.