Improved function and myocardial repair of infarcted heart by intracoronary injection of mesenchymal stem cell-derived growth factors

Ba Khoi Nguyen, Simon Maltais, Louis P. Perrault, Jean François Tanguay, Jean Claude Tardif, Louis Mathieu Stevens, Mélanie Borie, François Harel, Samer Mansour, Nicolas Noiseux

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Transplantation of mesenchymal stem cells (MSC) improves repair and function recovery following myocardial infarction (MI), but underlying mechanisms remain to be elucidated. We hypothesize that MSC could achieve protection by paracrine effects through released mediators rather than direct cardiac regeneration. We sought to characterize the effects of MSC-secreted growth factors on extent of early recovery from MI. Swine subjected to acute MI by temporary balloon occlusion of the left anterior descending coronary artery using percutaneous techniques received intracoronary injection of either concentrated MSC-derived growth factors or control medium. Animals were killed at 7 days to evaluate early effects. Treatment with MSC-derived factors significantly reduced cardiac troponin-T elevation and improved echocardiographic parameters, including fractional area shortening, stroke volume, cardiac output, and wall motion score index. Quantitative evaluation of fibrosis by Verhoff staining revealed a reduction of the fibrotic area in the infarcted zone. Similarly, Masson's trichrome staining revealed reduced myocardial damage as demonstrated by areas of relatively preserved myocardium in the infarcted area. TUNEL assay demonstrated less cardiomyocyte apoptosis. Protein array detected the presence of angiogenic (vascular endothelial growth factor, endothelin, and epiregulin), anti-apoptotic (Galectin-3, Smad-5, sRFP-1, and sRFP-4) and anti-remodeling factors. Reverse transcription polymerase chain reaction confirmed the expression of these factors. In summary, a single intracoronary injection of concentrated biologically active factors secreted by MSC could achieve early protection of ischemic myocardium and improve cardiac repair and contractility. MSC-derived growth factors injection (rather than MSC themselves) should be evaluated as a novel therapy to treat ischemic heart disease, avoiding many practical and technical issues of cell therapy.

Original languageEnglish (US)
Pages (from-to)547-558
Number of pages12
JournalJournal of cardiovascular translational research
Volume3
Issue number5
DOIs
StatePublished - Oct 1 2010

Keywords

  • Cardiac Function
  • Cellular Therapy
  • Growth Factors
  • Myocardial Ischemia
  • Stem Cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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