Efficacy comparison between intraportal and subcapsular islet transplants in a murine diabetic model.

ABSTRACT

BACKGROUND: It is important to determine the efficacy of intraportal (IP) islet transplantation in comparison with other transplant sites. In this study, we sought to determine the optimal number of islets to achieve normoglycemia following transplantation into the liver versus the kidney using a mouse model. METHODS: Streptozotocin-induced diabetic mice (Balb/C) were transplanted with syngeneic islets via the IP versus renal subcapsular (SC) routes. The transplanted islet numbers were 0 to 800 (n = 3-5). We assessed the correlation between parameters and islet numbers, comparing IP versus SC groups. The parameters were (1) percentage of normoglycemia; (2) postoperative days to normoglycemia; (3) mean blood glucose levels at various points from pretransplantation to the end of the study (postoperative day 28); (4) mean serum insulin; and (5) area under the curve of blood glucose levels after glucose injection. RESULTS: Two hundred islets yielded normoglycemia in renal subcapsular grafts, while 800 islets were the minimum required for normoglycemia with IP transplantation. The transplant efficacy in SC transplantation was 2 to 5 times greater than that of IP transplantation. The days to normoglycemia were significantly different between IP versus renal SC islets (13.25 +/- 4.38 days vs 4.50 +/- 0.81 days; P = .007). CONCLUSION: The efficacy of islet transplantation in murine diabetic models was significantly greater under the kidney capsule. Clinical islet transplantation could benefit from trials of alternative transplant sites.