High Fractions of Large Islets in Human Islet Preparations Detrimentally Affect Posttransplant Outcomes in Streptozotocin-Induced Diabetic Immunodeficient Mice.

Objectives: The aim of this study was to determine whether the size of islets isolated from human donors-measured pretransplant-impacts transplantation outcomes in diabetic mice.

Methods: Human islets (1200 islet equivalents) were transplanted into the kidney capsules of streptozotocin-induced diabetic immunodeficient mice. Data from a total of 174 mice that received islets from 45 isolations were analyzed to evaluate the correlation between pretransplant islet size and posttransplant diabetes reversal. Fluorescent images of islet clusters were used to categorize individual islets by size (small, 50-150 μm; medium, 150-250 μm; large, >250 μm), and the fractions of islets in each category were calculated.

Results: The fraction of large islets negatively correlated with diabetes reversal rates. Mice that received islet grafts containing 0% to 5%, 5% to 10%, and more than 10% large islets had diabetes reversal rates of 75%, 61%, and 45%, respectively (P = 0.0112). Furthermore, mice that exhibited diabetes reversal received smaller fractions of large islets than mice that did not (5.5% vs 8.0%, P = 0.0003). Intriguingly, the fractions of medium and small islets did not correlate with diabetes reversal outcomes.

Conclusions: The fraction of large islets is a sensitive predictor of human islet transplantation outcomes in diabetic mice.