title: Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.
abstract: The mechanism for stem cell-mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofibre network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibres presenting heparin were capable of binding paracrine factors from a medium phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischaemia-reperfusion model of acute myocardial infarction, we found significant preservation of haemodynamic function. Through media manipulation, we were able to determine that crucial factors are primarily < 30 kDa and primarily heparin-binding. Using recombinant VEGF- and bFGF-loaded nanofibre networks, the effect observed with conditioned media was recapitulated. When evaluated in another disease model, a chronic rat ischaemic hind limb, our factor-loaded materials contributed to extensive limb revascularization. These experiments demonstrate the potency of the paracrine effect associated with stem cell therapies and the potential of a biomaterial to bind and deliver these factors, pointing to a potential therapy based on synthetic materials and recombinant factors as an acellular therapy.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Han
authors.forename: S N Prasanna
authors.initials: SN
authors.lastname: Murthy
authors.forename: Kanya
authors.initials: K
authors.lastname: Rajangam
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.forename: Jon W
authors.initials: JW
authors.lastname: Lomasney
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000628:therapy*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006352:Heart Ventricles / Q000503:physiopathology; D006493:Heparin / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D057139:Nanofibers / Q000737:chemistry*; D019899:Paracrine Communication / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D006493:Heparin