Effect of low-temperature culture and site of transplantation on hamster islet xenograft survival (hamster to mouse)

Abstract

Isolated hamster islets were transplanted either into the liver via the portal vein or into the renal subcapsular space of diabetic C57BL/6J mice. The mean survival time (MST) of hamster islets cultured overnight at 37 degrees C was 8.5 +/- 0.6 days when transplanted into the liver as compared to an MST of greater than 21.7 +/- 4.9 days with 1 recipient still normoglycemic at 60 days when the islets were placed in the renal subcapsular space. Low-temperature culture (24 degrees C) of the hamster islets for 7 days produced a further significant prolongation of xenograft survival when the islets were placed beneath the renal capsule (MST greater than 43.3 +/- 4.7 days) with 2 recipients normoglycemic at 60 days. A single injection of anti-T-lymphocyte serum in conjunction with low-temperature culture did not produce a further increase in MST; however, 3 recipients were normoglycemic at 60 days. Removal of the kidney bearing successful xenografts at 60 days resulted in a rapid return to the diabetic state. It was interesting that the xenografts maintained normoglycemia in the mice at a level equivalent to the normal hamster (66.2 +/- 4.7 mg/dl) instead of the nonfasting level found in normal C57BL/6J mice (128.4 +/- 6.4 mg/dl). The findings indicate that low-temperature culture of the donor islets in conjunction with using the renal capsule as the site of transplantation produced a marked prolongation of hamster islet xenograft survival. Slow rejection of the xenografts did occur in this site, and histologic studies indicated that this rejection may be antibody mediated.