Document Detail

Inducing local T cell apoptosis with anti-Fas-functionalized polymeric coatings fabricated via surface-initiated photopolymerizations.
MedLine Citation:
PMID:  20138358     Owner:  NLM     Status:  MEDLINE    
Cell encapsulation has long been investigated as a means to achieve transplant immunoprotection as it creates a physical barrier between allograft tissue and host immune cells. Encapsulation with passive barrier materials alone, however, is generally insufficient to protect donor tissue from rejection, because small cytotoxic molecules produced by activated T cells can diffuse readily into the capsule and mediate allograft death. As a means to provide bioactive protection for polymeric encapsulation devices, we investigated a functionalized polymeric coating that mimics a natural T cell regulation pathway. T cells are regulated in vivo via Fas, a well-known 'death receptor,' whereby effector cells express Fas ligand and elicit T cell apoptosis upon binding the Fas receptor on a T cell surface. Anti-Fas antibodies are capable of replicating this effect and induce T cell apoptosis in solution. Here, an iniferter-based living radical polymerization was utilized to fabricate surface-anchored polymer chains containing poly(ethylene glycol) with covalently incorporated pendant anti-Fas antibody. Using this reaction mechanism, we demonstrate fabrication conditions that yield surface densities in excess of 1.5 ng/cm(2) of incorporated therapeutic, as detected by ELISA. Additionally, we show that coatings containing anti-Fas antibody induced significant T cell apoptosis, 21+/-2% of cells, after 24h. Finally, the incorporation of a T cell adhesion ligand, intracellular adhesion molecule-1, along with anti-Fas antibody, yielded even higher levels of apoptosis, 34+/-1% of T cells, compared to either signal alone.
Patrick S Hume; Kristi S Anseth
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-06-03     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  3166-74     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
Antigens, CD95 / antagonists & inhibitors,  immunology*
Cell Adhesion
Enzyme-Linked Immunosorbent Assay
Jurkat Cells
Polymers / chemistry*
T-Lymphocytes / cytology*
Grant Support
R01 DK076084/DK/NIDDK NIH HHS; R01 DK076084-02/DK/NIDDK NIH HHS; R01DK076084/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Antigens, CD95; 0/Polymers

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