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

Authors

  • Matthew J. Webber,

    1. Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
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  • Xiaoqiang Han,

    1. Department of Pathology, Northwestern University, Chicago, IL, USA
    2. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • S. N. Prasanna Murthy,

    1. Department of Pathology, Northwestern University, Chicago, IL, USA
    2. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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  • Kanya Rajangam,

    1. Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
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  • Samuel I. Stupp,

    1. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    2. Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA
    3. Department of Chemistry, Northwestern University, Evanston, IL, USA
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  • Jon W. Lomasney

    Corresponding author
    1. Department of Pathology, Northwestern University, Chicago, IL, USA
    2. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    • Northwestern University Feinberg School of Medicine, Ward 3-210, 303 East Chicago Avenue, Chicago, IL 60611, USA.
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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. Copyright © 2010 John Wiley & Sons, Ltd.

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