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Biomolecular surface engineering of pancreatic islets with thrombomodulin

Paper ID Volume ID Publish Year Pages File Format Full-Text
1390 83 2010 9 PDF Available
Title
Biomolecular surface engineering of pancreatic islets with thrombomodulin
Abstract

Islet transplantation has emerged as a promising treatment for Type 1 diabetes, but its clinical impact remains limited by early islet destruction mediated by prothrombotic and innate inflammatory responses elicited upon transplantation. Thrombomodulin (TM) acts as an important regulator of thrombosis and inflammation through its capacity to channel the catalytic activity of thrombin towards generation of activated protein C (APC), a potent anticoagulant and anti-inflammatory agent. We herein describe a novel biomolecular strategy for re-engineering the surface of pancreatic islets with TM. A biosynthetic approach was employed to generate recombinant human TM (rTM) bearing a C-terminal azide group, which facilitated site-specific biotinylation of rTM through Staudinger ligation. Murine pancreatic islets were covalently biotinylated through targeting of cell surface amines and aldehydes and both islet viability and the surface density of streptavidin were maximized through optimization of biotinylation conditions. rTM was immobilized on islet surfaces through streptavidin–biotin interactions, resulting in a nearly threefold increase in the catalytic capacity of islets to generate APC.

Keywords
Islet transplantation; Thrombomodulin; Cell surface engineering; Staudinger ligation
First Page Preview
Biomolecular surface engineering of pancreatic islets with thrombomodulin
Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 6, Issue 6, June 2010, Pages 1895–1903
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering