Molecular and Cellular Biochemistry

, Volume 392, Issue 1–2, pp 187–204 | Cite as

Human mesenchymal stem cells express a myofibroblastic phenotype in vitro: comparison to human cardiac myofibroblasts

  • Melanie A. Ngo
  • Alison Müller
  • Yun Li
  • Shannon Neumann
  • Ganghong Tian
  • Ian M. C. Dixon
  • Rakesh C. Arora
  • Darren H. Freed
Article

Abstract

Cardiac fibrosis accompanies a variety of myocardial disorders, and is induced by myofibroblasts. These cells may be composed of a heterogeneous population of parent cells, including interstitial fibroblasts and circulating progenitor cells. Direct comparison of human bone marrow-derived mesenchymal stem cells (BM-MSCs) and cardiac myofibroblasts (CMyfbs) has not been previously reported. We hypothesized that BM-MSCs readily adopt a myofibroblastic phenotype in culture. Human primary BM-MSCs and human CMyfbs were isolated from patients undergoing open heart surgery and expanded under standard culture conditions. We assessed and compared their phenotypic and functional characteristics by examining their gene expression profile, their ability to contract collagen gels and synthesize collagen type I. In addition, we examined the role of non-muscle myosin II (NMMII) in modulating MSC myogenic function using NMMII siRNA knockdown and blebbistatin, a specific small molecule inhibitor of NMMII. We report that, while human BM-MSCs retain pluripotency, they adopt a myofibroblastic phenotype in culture and stain positive for the myofibroblast markers α-SMA, vimentin, NMMIIB, ED-A fibronectin, and collagen type 1 at each passage. In addition, they contract collagen gels in response to TGF-β1 and synthesize collagen similar to human CMyfbs. Moreover, inhibition of NMMII activity with blebbistatin completely attenuates gel contractility without affecting cell viability. Thus, human BM-MSCs share and exhibit similar physiological and functional characteristics as human CMyfbs in vitro, and their propensity to adopt a myofibroblast phenotype in culture may contribute to cardiac fibrosis.

Keywords

Cardiac fibrosis Stem cell differentiation Myofibroblast contractility Blebbistatin Cellular contraction Wound healing 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Melanie A. Ngo
    • 1
  • Alison Müller
    • 1
  • Yun Li
    • 1
  • Shannon Neumann
    • 1
  • Ganghong Tian
    • 3
  • Ian M. C. Dixon
    • 1
  • Rakesh C. Arora
    • 1
    • 2
    • 3
  • Darren H. Freed
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research CentreUniversity of ManitobaWinnipegCanada
  2. 2.Department of Surgery, Section of Cardiac Surgery, St. Boniface General Hospital Cardiac Sciences ProgramUniversity of ManitobaWinnipegCanada
  3. 3.Cardiac StudiesNational Research Council - Institute for BiodiagnosticsWinnipegCanada
  4. 4.Cardiac Sciences ProgramSt. Boniface General HospitalWinnipegCanada

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