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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02032005-141942 |
| Date | 03 February 2005 |
| Creators | Roth, David |
| Contributors | Dr. Taylor Wang |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02032005-141942/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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