A Novel Method of Monitoring Response to Islet Transplantation: Bioluminescent Imaging of an NF-kB Transgenic Mouse Model

Background. Transplantation of encapsulated pancreatic islets is a novel therapeutic approach for the treatment of Type 1 diabetes mellitus that has the potential to circumvent both a limited islet supply and immunosuppression. Current methods for scoring the biocompatibility of the alginate-based capsules that sequester Islets of Langerhans include fabrication and implantation into the peritoneal cavity of mice, incubation, retrieval via peritoneal lavage, and observationofthenumberofcellsorcelllayerssurroundingthecapsules.Thismethodallowsonlyonedatapointtobe obtained per animal. We describe a method to measure biocompatibility real time and in situ. This method of monitoring immune response using bioluminescent technology and a nuclear factor-kappa beta (NF-kB) sensitive transgenic mouse model allows many data points to be acquired per animal, reduces the number of animals required to obtain statistically significant immune response data over time, and in turn reduces error associated with animal variability.NF-kBisatranscriptionfactorthatcoordinatestheinflammatoryandwoundhealingcascadesbyinitiating the transcription of cytokines, chemokines, adhesion molecules, and proinflammatory genes. Methods. Inflammation after the transplantation of five types of capsules was monitored for 6 six weeks after transplantation into the dorsal-cervical fat pad. Results. Bioluminescence over 6-week time period: Capsule group 1.0.00 normalized units 2 , Bead group 1.3.26 normalized units 2 , No coat group .96.48 normalized units 2 , Sham group .96.00 normalized units 2 , Control group .17.11 normalized units 2 .