title: In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection.
abstract: BACKGROUND
  Bioluminescence imaging (BLI) modalities are being developed to monitor islet transplant mass and function in vivo. The aim of this study was to use the BLI system to determine how the change in functional islet mass correlated to metabolic abnormalities during the course of alloimmune rejection in a murine transplant model.
  
  
  METHODS
  Islets obtained from a transgenic mouse strain (FVB/NJ-luc) that constitutively expressed firefly luciferase were transplanted to various implantation sites of syngeneic wild-type FVB/NJ or allogeneic Balb/C streptozotocin-induced diabetic recipients. In vivo graft luminescent signals were repeatedly measured after transplantation using the BLI system and related to blood glucose levels and graft site histologic findings.
  
  
  RESULTS
  The BLI signals were detected in as few as 10 islets implanted in the renal subcapsular space, intrahepatic, intraabdominal, and subcutaneous locations. There was a linear relationship between the number of islets transplanted and luminescence intensity. In isografts, stable luminescence intensity signals occurred within 2 weeks of transplantation and remained consistent on a long-term basis (18 months) after transplantation. In allografts, after normoglycemia was achieved and stable luminescence intensity occurred, graft bioluminescent intensity progressively decreased several days before permanent recurrence of hyperglycemia as a result of histologically proven rejection ensued.
  
  
  CONCLUSIONS
  Bioluminescence imaging is a sensitive method for tracking the fate of islets after transplantation and is a useful method to detect early loss of functional islet mass caused by host immune responses even before overt metabolic dysfunction is evident. Bioluminescence imaging holds promise for use in designing and testing interventions to prolong islet graft survival.
authors.affiliation: Department of Surgery, Division of Organ Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Courtney S
authors.initials: CS
authors.lastname: Larson
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Baker
authors.forename: Dixon B
authors.initials: DB
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D042241:Early Diagnosis; D006084:Graft Rejection / Q000175:diagnosis*; D007150:Immunohistochemistry; D016381:Islets of Langerhans Transplantation; D049409:Luciferases, Firefly; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012015:Reference Standards; D014184:Transplantation, Homologous
chemical_list: D049409:Luciferases, Firefly