Prolonging Islet Allograft Survival Using In Vivo Bioluminescence Imaging to Guide Timing of Antilymphocyte Serum Treatment of Rejection

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Abstract
Background. Bioluminescence imaging (BLI) is a sensitive and noninvasive method for tracking the fate of transplanted islets. The aim of this study was to investigate whether early detection of rejection by BLI can aid in the timing of antilymphocyte serum (ALS) treatment for prolonging islet graft survival. Methods. Transgenic islets (200 per recipient) expressing the firefly luciferase from FVB/NJ strain (H-2q) mice were transplanted under the kidney capsule of streptozotocin-induced diabetic allogeneic Balb/c strain (H-2d) mice. BLI signals and serum glucose levels were measured daily after transplant. Four groups of mice were transplanted: group 1 recipients were untreated controls (n=12), group 2 (n=8) received ALS before transplant, group 3 (n=10) received ALS at a time after transplant when normoglycemic but prompted by a reduction (∼30%) in BLI signal intensity for 2 consecutive days, and group 4 (n=5) received ALS after transplant when prompted by blood glucose levels increasing ∼20% from the normoglycemic baseline (BLI reduction ∼70%). Results. The incidence of graft loss from rejection in groups 1, 2, 3, and 4 was 92.3%, 88%, 40%, and 100%, respectively. The mean (±SE) time to graft loss in groups 1, 2, 3 and 4 was 22.5±4.8, 29.2±9.9, 53.5±17.9, and 22.1±2.4 days, respectively. Conclusions. Noninvasive imaging modalities of functional islet mass, such as BLI (but not blood glucose levels), can prompt the appropriate timing of ALS treatment of islet allograft rejection and significantly prolong graft survival or protect the grafts from permanent loss.