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Potential for Immunoprotection of Pancreatic Islets by Covalent Modification with Poly(ethylene glycol)

Engman, Carl L (2002) Potential for Immunoprotection of Pancreatic Islets by Covalent Modification with Poly(ethylene glycol). Master's Thesis, University of Pittsburgh. (Unpublished)

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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 student's 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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Engman, Carl Lclest19@pitt.eduCLEST19
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWagner,
Committee MemberRussell,
Committee MemberBeckman,
Date: 23 December 2002
Date Type: Completion
Defense Date: 5 December 2002
Approval Date: 23 December 2002
Submission Date: 12 December 2002
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: MSBeng - Master of Science in Bioengineering
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Diabetes Mellitus; ELISA; immunoprotection; pancreatic islets; transplantation
Other ID:, etd-12122002-184910
Date Deposited: 10 Nov 2011 20:10
Last Modified: 15 Nov 2016 13:54


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