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

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.

• 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)
• 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

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)