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 NoiseuxEmail author


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.


Cardiac Function Cellular Therapy Growth Factors Myocardial Ischemia Stem Cells 



We acknowledge Dr. D.C. Roy (Hôpital Maisonneuve-Rosemont) for his contribution in flow cytometric analyses. We thank M.P. Mathieu, E. Reny-Nolin, S. Gilligan, P. Geoffroy, and D. Lauzier for their precious help in this study and Dr Yan Fen Shi for the echocardiographic analysis. Drs. Noiseux and Perrault are scholars of Fonds de la Recherche en Santé du Québec (FRSQ). Dr. Noiseux and Perrault are supported by the Heart and Stroke Foundation of Québec, and Department of Surgery, Université de Montréal. Dr Stevens is supported by the Canadian Institutes of Health Research (CIHR).


No conflict of interest to disclose.

Supplementary material

12265_2010_9171_MOESM1_ESM.doc (42 kb)
Supplementary data (DOC 42 kb)
12265_2010_9171_Fig6_ESM.jpg (409 kb)
Supplementary figure Echocardiographic analysis up to 28 days. A Intracoronary injection of MSC-derived growth factors after acute MI had persistent favorable effects on cardiac function as revealed by a significantly improved WMSI, used as an indicator of LV function and contractility (P < 0.001). B Similarly, LVEF tended to be worst in the control group (P = 0.072). Number of animals: n = 11 and 12 at baseline, n = 5 at 3 days, n = 6 and 7 at 7 days, and n = 3 at 30 days for controls and MSC-CM, respectively. Statistical analyses were made using longitudinal mixed effect models (JPEG 408 kb) (JPEG 408 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ba-Khoi Nguyen
    • 1
  • Simon Maltais
    • 2
  • Louis P. Perrault
    • 2
  • Jean-François Tanguay
    • 3
  • Jean-Claude Tardif
    • 3
  • Louis-Mathieu Stevens
    • 1
    • 4
  • Mélanie Borie
    • 4
  • François Harel
    • 5
  • Samer Mansour
    • 4
    • 6
  • Nicolas Noiseux
    • 1
    • 4
    • 7
    Email author
  1. 1.Cardiac SurgeryMontreal University Hospital Centre (CHUM)MontrealCanada
  2. 2.Cardiac SurgeryMontreal Heart InstituteMontrealCanada
  3. 3.CardiologyMontreal Heart InstituteMontrealCanada
  4. 4.CHUM Research Center (CRCHUM)MontréalCanada
  5. 5.Nuclear MedicineMontreal Heart InstituteMontrealCanada
  6. 6.CardiologyCHUMMontrealCanada
  7. 7.CHUM Hôtel-Dieu de MontréalMontréalCanada

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