Document Detail


Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation.
MedLine Citation:
PMID:  19782393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pancreatic islet encapsulation within semi-permeable materials has been proposed for transplantation therapy of type I diabetes mellitus. Polymer hydrogel networks used for this purpose have been shown to provide protection from islet destruction by immunoreactive cells and antibodies. However, one of the fundamental deficiencies with current encapsulation methods is that the permselective barriers cannot protect islets from cytotoxic molecules of low molecular weight that are diffusible into the capsule material, which subsequently results in beta-cell destruction. Use of materials that can locally inhibit the interaction between the permeable small cytotoxic factors and islet cells may prolong the viability and function of encapsulated islet grafts. Here we report the design of anti-inflammatory hydrogels supporting islet cell survival in the presence of diffusible pro-inflammatory cytokines. We demonstrated that a poly(ethylene glycol)-containing hydrogel network, formed by native chemical ligation and presenting an inhibitory peptide for islet cell surface IL-1 receptor, was able to maintain the viability of encapsulated islet cells in the presence of a combination of cytokines including IL-1 beta, TNF-alpha, and INF-gamma. In stark contrast, cells encapsulated in unmodified hydrogels were mostly destroyed by cytokines which diffused into the capsules. At the same time, these peptide-modified hydrogels were able to efficiently protect encapsulated cells against beta-cell specific T-lymphocytes and maintain glucose-stimulated insulin release by islet cells. With further development, the approach of encapsulating cells and tissues within hydrogels presenting anti-inflammatory agents may represent a new strategy to improve cell and tissue graft function in transplantation and tissue engineering applications.
Authors:
Jing Su; Bi-Huang Hu; William L Lowe; Dixon B Kaufman; Phillip B Messersmith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-25
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-02-17     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  308-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Culture Techniques / methods*
Cell Death / drug effects
Cell Line, Tumor
Cell Separation
Cell Survival / drug effects
Cross-Linking Reagents / pharmacology
Cytokines / metabolism
Cytoprotection / drug effects
Glucose / pharmacology
Hydrogels / chemistry,  pharmacology*
Inflammation Mediators / metabolism
Insulin / secretion
Insulin-Secreting Cells / cytology*,  drug effects*,  immunology,  secretion
Mice
Peptides / chemistry,  pharmacology*
T-Lymphocytes, Cytotoxic / cytology,  drug effects
Grant Support
ID/Acronym/Agency:
R01 DE013030/DE/NIDCR NIH HHS; R01 DE013030-09/DE/NIDCR NIH HHS; R01 EB003806/EB/NIBIB NIH HHS; R01 EB003806/EB/NIBIB NIH HHS; R01 EB003806-05/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cross-Linking Reagents; 0/Cytokines; 0/Hydrogels; 0/Inflammation Mediators; 0/Insulin; 0/Peptides; IY9XDZ35W2/Glucose
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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