Abstract |
The CXC chemokine stromal cell-derived factor-1α (SDF-1α, CXCL12) has been proven to recruit CXCR4 positive stem and progenitor cells of different sources to defected heart sites, with significant clinical benefits. However, the rapid proteolytic inactivation by inflammation-related proteases, inaccurate drug delivery or inappropriate local concentrations belong to the largest disadvantages for feasible application. Herein, we present a switchable, biased-like SDF-1α variant, AAV-[S4V]-SDF-1α, whose distinct activity is coupled to the inflammation-associated presence of dipeptidylpeptidase-4 (DPP-4), which cleaves an alanine- alanine dipeptide from the precursor. We decorated starPEG- heparin hydrogels with our novel SDF-1α variant and tested them for immobilization efficiency, time-dependent protein release as well as mobilization of early endothelial progenitor cells (eEPCs) in vitro. We found higher migration rates compared to conventional SDF-1α. In summary, we provide a conceptual work on cooperative effects of enzymatically activatable SDF-1α and starPEG- heparin hydrogels.
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Authors | Lars Baumann, Silvana Prokoph, Christian Gabriel, Uwe Freudenberg, Carsten Werner, Annette G Beck-Sickinger |
Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 162
Issue 1
Pg. 68-75
(Aug 20 2012)
ISSN: 1873-4995 [Electronic] Netherlands |
PMID | 22634073
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier B.V. All rights reserved. |
Chemical References |
- Chemokine CXCL12
- Hydrogels
- Recombinant Proteins
- Polyethylene Glycols
- Heparin
- Dipeptidyl Peptidase 4
- Pancreatic Elastase
- Matrix Metalloproteinase 9
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Topics |
- Animals
- COS Cells
- Cell Movement
(drug effects)
- Cells, Cultured
- Chemokine CXCL12
(administration & dosage, metabolism, pharmacology)
- Chlorocebus aethiops
- Chromatography, Affinity
- Dipeptidyl Peptidase 4
(metabolism)
- Endothelial Cells
(cytology, drug effects)
- Heparin
(chemistry, metabolism)
- Humans
- Hydrogels
(chemistry, metabolism)
- Jurkat Cells
- Matrix Metalloproteinase 9
(metabolism)
- Pancreatic Elastase
(metabolism)
- Polyethylene Glycols
(chemistry, metabolism)
- Recombinant Proteins
(administration & dosage, metabolism, pharmacology)
- Stem Cells
(cytology, drug effects)
- Tissue Scaffolds
(chemistry)
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