title: Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells.
abstract: Enrichment of progenitor cells in ischemic tissue has become a promising therapeutic strategy in the treatment of myocardial infarction. Towards this aim, we report a biology-inspired concept using sulfated glycosaminoglycans to sustainably generate chemokine gradients for the localized accumulation of early endothelial progenitor cells (eEPCs). StarPEG-heparin hydrogels, which have been previously demonstrated to support angiogenesis, were functionalized with SDF-1α, a potent chemoattractant known to act on EPCs. The gels were quantitatively shown to release the chemokine in amounts that are adjustable by the choice of loading concentrations and by matrix metalloprotease (MMP) mediated hydrogel cleavage. Transwell assays confirmed significantly enhanced migration of early EPCs towards concentration gradients of hydrogel-delivered SDF-1α in vitro. Subcutaneous implantation of SDF-1α-releasing gels in mice resulted in massive infiltration of early EPCs and subsequently improved vascularization. In conclusion, sustained delivery of SDF-1α from pro-angiogenic starPEG-heparin hydrogels can effectively attract early EPCs, offering a powerful means to trigger endogenous mechanisms of cardiac regeneration.
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Technische Universität Dresden, Center for Regenerative Therapies Dresden, 01069 Dresden, Germany.
authors.forename: Silvana
authors.initials: S
authors.lastname: Prokoph
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Chavakis
authors.forename: Kandice R
authors.initials: KR
authors.lastname: Levental
authors.forename: Andrea
authors.initials: A
authors.lastname: Zieris
authors.forename: Uwe
authors.initials: U
authors.lastname: Freudenberg
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D054377:Chemokine CXCL12; D020100:Hydrogels; D006493:Heparin