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

Matthew J. Webber, Xiaoqiang Han, S. N. Prasanna Murthy, Kanya Rajangam, Samuel I. Stupp, Jon W. Lomasney

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)600-610
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume4
Issue number8
DOIs
Publication statusPublished - Dec 1 2010

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Keywords

  • biomaterials
  • bionanotechnology
  • myocardial infarction
  • paracrine effect
  • peptide amphiphiles
  • regenerative medicine
  • stem cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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