Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases

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 nanofiber 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 nanofibers presenting heparin were capable of binding paracrine factors from a media phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischemia-reperfusion model of acute myocardial infarction, we found significant preservation of hemodynamic function. Through media manipulation, we were able to determine that crucial factors are primarily less than 30 kDa and primarily heparin-binding. Using recombinant VEGF and bFGF loaded nanofiber networks the effect observed with conditioned media was recapitulated. When evaluated in another disease model, a chronic rat ischemic 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.