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

• DOI: 10.1002/term.273
• Publication Date: 2010-03-10T09:55:35Z
• Authors: Matthew J. Webber; Xiaoqiang Han; S. N. Prasanna Mu...; Kanya Rajangam; Samuel I. Stupp; Jon W. Lomasney
• Keywords: Vascular Endothelial Growth Factor A; 0301 basic medicine; Heparin; Heart Ventricles; Myocardial Infarction; Nanofibers; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Myocardial Contraction; Hindlimb; Rats; 3. Good health; Molecular Weight; Mice; 03 medical and health sciences; Cardiovascular Diseases; Culture Media, Conditioned; Paracrine Communication; Animals; Fibroblast Growth Factor 2; Peptides

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.