Diabetes Mellitus is one of the predominant contributors to morbidity and mortality worldwide. Prior to the advent of insulin therapy, patients suffering from Type I diabetes generally did not survive past childhood. Even with insulin therapy, a physiologically normal insulin response to increased systemic glucose cannot be achieved. Pancreatic islet transplantation has been shown to restore the physiological response to glucose, but risks associated with chronic immune suppression outweigh the benefit of tighter glucose regulation. This study investigates the potential of covalent modification of pancreatic islets with poly(ethylene glycol) (PEG) to abrogate the immune response towards transplanted islets and eliminate the need for chronic immune suppression. Previous studies have shown that PEG can be covalently bound to islet extracellular matrix (ECM) and surface proteins with no adverse affect on islet viability or function. The goal of this study was to determine the effect of covalent PEG modification on binding of islet-specific antibody, and to determine whether or not PEG modification could prolong graft survival in vivo. By a novel adaptation of an enzyme-linked immunosorbent assay (ELISA) the amount of islet-specific antibody bound to unmodified or PEG-modified islets was compared semi-quantitatively. Islets treated with 40kD branched PEG-NHS bound significantly more antibody than untreated controls. Based on the students paired t-test there was no statistically significant change in antibody binding between 5kD PEG-treated and unmodified islets, although 7 of 9 PEG treated groups in this experiment bound less antibody than the corresponding unmodified groups. For in vivo islet transplantation , there was no difference in graft survival observed between PEG-treated and untreated grafts. Although PEG treatment did not have an apparent effect on in vivo graft survival, the effects observed in the antibody binding experiment suggest that PEG does modify antibody binding and further investigation of this technique is warranted.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12122002-184910 |
| Date | 23 December 2002 |
| Creators | Engman, Carl L |
| Contributors | Dr. Alan Russell, Dr. Eric Beckman, Dr. William Wagner |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu:80/ETD/available/etd-12122002-184910/ |
| 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 University of Pittsburgh 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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