Journal
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 4, Issue 8, Pages 600-610Publisher
WILEY
DOI: 10.1002/term.273
Keywords
regenerative medicine; myocardial infarction; paracrine effect; biomaterials; bionanotechnology; stem cells; peptide amphiphiles
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Funding
- US Army Telemedicine and Advanced Technology Research Center (TATRC) [W81XWH-05-1-0381]
- Northwestern University
- NIH [5T90-DA022881]
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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 bEGF-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. Copyright (C) 2010 John Wiley & Sons, Ltd.
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