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Title page for ETD etd-02032005-141942


Type of Document Master's Thesis
Author Roth, David
Author's Email Address dave.roth@vanderbilt.edu
URN etd-02032005-141942
Title Bioluminescent imaging of an NF-kB transgenic mouse model for monitoring immune response to a bioartificial pancreas real time and in vivo: validation of the method
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Dr. Taylor Wang Committee Chair
Keywords
  • bioartifical pancreas
  • NF-kB
  • cellular encapsulation
Date of Defense 2005-02-04
Availability unrestricted
Abstract
Cell encapsulation is a novel therapeutic approach for the treatment of Type I Diabetes Mellitus that circumvents both the immunosuppression and limited allograft donor source dilemma. 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 for specified periods of time, retrieval via peritoneal lavage, and observation of the number of cells or cell layers surrounding the capsules. This method allows only one data point to be obtained per animal. In this experiment we propose to measure biocompatibility real time and in vivo This new method of monitoring immune response using bioluminescent technology and a Nuclear Factor-kappa Beta sensitive transgenic mouse model allows unlimited 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-kB is a transcription factor that plays a critical upstream role in the coordination of the inflammatory and would healing cascades by initiating the transcription of many cytokines, chemokines, adhesion molecules, and proinflammatory genes. Five types of capsules were monitored over 6 six weeks after transplantation into the dorsal-cervical fat pad, a capsule group, a bead group, a non-coated capsule group, a sham surgery group, and a control group. The bead, capsule, and non-coated capsule transplant groups allow the effects of capsule size and capsule wall composition on NF-kB activity to be monitored. This imaging modality was able to detect statistically significant differences in NF-kB activity between pre and post-operative data points per mouse. It was also able to discern with significance an unexpected increase in NF-kB activity due to capsule size instead of capsule wall composition over a six week time period.
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