Applied Biochemistry and Biotechnology

, Volume 186, Issue 1, pp 245–255 | Cite as

MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to Cardiomyocytes

  • Vajiheh Neshati
  • Samaneh Mollazadeh
  • Bibi Sedigheh Fazly BazzazEmail author
  • Antoine A. F. de Vries
  • Majid Mojarrad
  • Hojjat Naderi-Meshkin
  • Zeinab Neshati
  • Mahdi Mirahmadi
  • Mohammad Amin Kerachian


Since the adult mammalian heart has limited regenerative capacity, cardiac trauma, disease, and aging cause permanent loss of contractile tissue. This has fueled the development of stem cell-based strategies to provide the damaged heart with new cardiomyocytes. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of self-renewal and differentiation into cardiomyocytes, albeit inefficiently. MicroRNAs (miRNAs, miRs) are non-coding RNAs that have the potential to control stem cell fate decisions and are employed in cardiac regeneration and repair. In this study, we tested the hypothesis that overexpression of miR-499a induces cardiomyogenic differentiation in BM-MSCs. Human BM-MSCs (hBM-MSCs) were transduced with lentiviral vectors encoding miR-499a-3p or miR-499a-5p and analyzed by immunostaining and western blotting methods 14 days post-transduction. MiR-499a-5p-transduced cells adopted a polygonal/rod-shaped (myocyte-like) phenotype and showed an increase in the expression of the cardiomyocyte markers α-actinin and cTnI, as cardiogenic differentiation markers. These results indicate that miR-499a-5p overexpression promotes the cardiomyogenic differentiation of hBM-MSCs and may thereby increase their therapeutic efficiency in cardiac regeneration.


MicroRNA-499a Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) Cardiomyogenesis Lentiviral vectors 



The authors are grateful to the members of the Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, the Netherlands, for their assistance in lentiviral vector construction and production and their helpful cooperation.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vajiheh Neshati
    • 1
  • Samaneh Mollazadeh
    • 1
  • Bibi Sedigheh Fazly Bazzaz
    • 2
    Email author
  • Antoine A. F. de Vries
    • 3
  • Majid Mojarrad
    • 4
    • 5
  • Hojjat Naderi-Meshkin
    • 6
  • Zeinab Neshati
    • 7
  • Mahdi Mirahmadi
    • 4
  • Mohammad Amin Kerachian
    • 4
    • 5
  1. 1.Biotechnology Research Center, Institute of Pharmaceutical TechnologyMashhad University of Medical SciencesMashhadIran
  2. 2.Biotechnology Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Department of CardiologyLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of Medical Genetics, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  5. 5.Medical Genetics Research Center, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  6. 6.Stem Cell and Regenerative Medicine Research DepartmentIranian Academic Center for Education, Culture Research (ACECR)MashhadIran
  7. 7.Department of Biology, Faculty of ScienceFerdowsi University of MashhadMashhadIran

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