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Updated: Jun 9, 2026
Transplantation of Pancreatic Islets Into the Kidney Capsule of Diabetic Mice
Published on: November 1, 2007
At what stage does pancreas allograft rejection become irreversible?: an experimental study
A Königsrainer1, W Mark, P Hechenleitner
1Department of Transplant Surgery, University of Innsbruck, Austria.
Background:
It is commonly believed that abnormal blood glucose levels indicate irreversible rejection. We were interested in determining the stage at which rejection remains reversible.
Methods:
A total of 54 Lewis rats were rendered diabetic with 55 mg/kg streptozocin and were then given a pancreas transplant from Brown Norway donors. Pancreatic juice was collected in a subcutaneous reservoir. All recipients received 15 mg/kg cyclosporine A (CsA) for 5 days. CsA was then discontinued for 2 days (n=7, group 1), 4 days (n=7, group 2), 6 days (n=9, group 3), 8 days (n=9, group 4), 9 days (n=11, group 5), and 10 days (n=11, group 6). Two animals of each group were euthanized at the end of the immunosuppressive-free interval, for histological assessment of the grade of rejection (G0, GI, GII, GIII). Rejection was treated with methylprednisolone (7 mg/kg body weight) and CsA (15 mg/kg body weight). The volume of pancreatic juice, together with juice cytology (C0, CI, CII) and blood glucose levels, was assessed daily.
Results:
Blood glucose remained normal throughout the observation period in animals with GI and GII rejection. The numbers of animals that became diabetic were as follows: 5 of 9 (group 4), 7 of 11 (group 5), and 8 of 11 (group 6). Decreased amounts of pancreatic juice were observed in all animals, except those in group 1. The histology returned to normal after anti-rejection therapy in four animals (57%) of group 1, in two animals (28%) of group 2, and in one animal (11%) of groups 3 and 4, respectively. Although there was no animal in groups 5 and 6 with normal graft histology after treatment, there were still four (36%) and three (27%) animals, respectively, that were normoglycemic and that had pancreatic grafts with well-preserved islets.
Conclusions:
From these data, we conclude that even GIII rejection with severe endothelialitis and isleitis can be reversed. Therefore, we suggest that a trial of enhanced immunosuppression is justified in patients with advanced pancreas allograft rejection.
