INTRACEREBRAL ALLOTRANSPLANTATION OF PURIFIED PANCREATIC ENDOCRINE CELLS AND PANCREATIC ISLETS IN DIABETIC RATS

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Abstract
Allogeneic pancreatic endocrine cells (PEC) and whole islets from inbred Lewis (AgB 1/1) and outbred Wistar rats were implanted intracerebrally (i.c.) into two designated areas of streptozotocin-induced diabetic ACI (AgB 4/4) rats across the major histocompatibility barrier. All the transplants of PEC from Lewis (n=12) and Wistar (n=7) donors remained functional for an observation period in excess of 200 days. In contrast, only 3/6 Lewis and 3/9 Wistar whole-islet transplants were able to maintain function for a prolonged period. Recipients with functional PEC or islet allografts had normalized nonfasting blood glucose (BG) in the 24-hr. BG profile, and they maintained a steady body weight gain. ACI recipients of PEC from Lewis rats had glucose disappearance K rates of 1.3±0.3 (mean ± SE) and a normal basal BG level in 4 hr following the i.v. glucose load. Histological section of the brain tissues with successful i.c. islet or PEC grafts up to a duration of 51/2 months revealed healthy endocrine cells in the cortex and the subarachnoid space. These grafts were permeated with capillaries but devoid of exocrine tissues or lymphoid cell infiltration. These observations suggest that the brain is an immunologically privileged site, and that it is a hospitable site for the pancreatic endocrine cell suspension. However, the immunological protection offered to allogeneic transplants by the brain is incomplete, and purified PEC must be employed to ensure consistent long-term allograft survival.

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