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

66 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 2010

Fingerprint

Nanofibers
Stem cells
Heparin
Cardiovascular Diseases
Stem Cells
Extremities
Myocardial Infarction
Hemodynamics
Biocompatible Materials
Conditioned Culture Medium
Cell- and Tissue-Based Therapy
Biomaterials
Peptides
Vascular Endothelial Growth Factor A
Reperfusion
Ligation
Rats
Coronary Vessels
Ischemia
Injections

Keywords

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

ASJC Scopus subject areas

  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Biomaterials

Cite this

Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. / Webber, Matthew J.; Han, Xiaoqiang; Prasanna Murthy, S. N.; Rajangam, Kanya; Stupp, Samuel I; Lomasney, Jon W.

In: Journal of Tissue Engineering and Regenerative Medicine, Vol. 4, No. 8, 12.2010, p. 600-610.

Research output: Contribution to journalArticle

Webber, Matthew J. ; Han, Xiaoqiang ; Prasanna Murthy, S. N. ; Rajangam, Kanya ; Stupp, Samuel I ; Lomasney, Jon W. / Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. In: Journal of Tissue Engineering and Regenerative Medicine. 2010 ; Vol. 4, No. 8. pp. 600-610.
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