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J Control Release. 2012 Aug 20;162(1):68-75. doi: 10.1016/j.jconrel.2012.04.049. Epub 2012 May 22.

A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro.

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1
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, Germany.

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.

PMID:
22634073
DOI:
10.1016/j.jconrel.2012.04.049
[Indexed for MEDLINE]

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