A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro.
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.
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, Germany.
Lars
L
Baumann
Silvana
S
Prokoph
Christian
C
Gabriel
Uwe
U
Freudenberg
Carsten
C
Werner
Annette G
AG
Beck-Sickinger
D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism; D019169:Jurkat Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry
D054377:Chemokine CXCL12; D020100:Hydrogels; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D006493:Heparin; D018819:Dipeptidyl Peptidase 4; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9