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Adult vascular smooth muscle cells in culture express neural stem cell markers typical of resident multipotent vascular stem cells

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Abstract

Differentiation of resident multipotent vascular stem cells (MVSCs) or de-differentiation of vascular smooth muscle cells (vSMCs) might be responsible for the SMC phenotype that plays a major role in vascular diseases such as arteriosclerosis and restenosis. We examined vSMCs from three different species (rat, murine and bovine) to establish whether they exhibit neural stem cell characteristics typical of MVSCs. We determined their SMC differentiation, neural stem cell marker expression and multipotency following induction in vitro by using immunocytochemistry, confocal microscopy, fluorescence-activated cell sorting analysis and quantitative real-time polymerase chain reaction. MVSCs isolated from rat aortic explants, enzymatically dispersed rat SMCs and rat bone-marrow-derived mesenchymal stem cells served as controls. Murine carotid artery lysates and primary rat aortic vSMCs were both myosin-heavy-chain-positive but weakly expressed the neural crest stem cell marker, Sox10. Each vSMC line examined expressed SMC differentiation markers (smooth muscle α–actin, myosin heavy chain and calponin), neural crest stem cell markers (Sox10+, Sox17+) and a glia marker (S100β+). Serum deprivation significantly increased calponin and myosin heavy chain expression and decreased stem cell marker expression, when compared with serum-rich conditions. vSMCs did not differentiate to adipocytes or osteoblasts following adipogenic or osteogenic inductive stimulation, respectively, or respond to transforming growth factor-β1 or Notch following γ-secretase inhibition. Thus, vascular SMCs in culture express neural stem cell markers typical of MVSCs, concomitant with SMC differentiation markers, but do not retain their multipotency. The ultimate origin of these cells might have important implications for their use in investigations of vascular proliferative disease in vitro.

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Authors and Affiliations

  1. Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin 9, Ireland

    Eimear Kennedy, Ciaran J. Mooney, Roya Hakimjavadi, Emma Fitzpatrick, Shaunta Guha & Paul A. Cahill

  2. Immunomodulation Research Group, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin 9, Ireland

    Laura E. Collins & Christine E. Loscher

  3. Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA

    David Morrow & Eileen M. Redmond

Authors
  1. Eimear Kennedy
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  2. Ciaran J. Mooney
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  3. Roya Hakimjavadi
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  4. Emma Fitzpatrick
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  5. Shaunta Guha
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  6. Laura E. Collins
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  7. Christine E. Loscher
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  8. David Morrow
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  9. Eileen M. Redmond
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  10. Paul A. Cahill
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Corresponding author

Correspondence to Paul A. Cahill.

Additional information

This study was supported in part by funds from Science Foundation Ireland (SFI-11/PI/1128 to P.A. Cahill) and the National Institutes of Health (R00HL095650 to D. Morrow and R21AA020365 to E.M. Redmond).

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Kennedy, E., Mooney, C.J., Hakimjavadi, R. et al. Adult vascular smooth muscle cells in culture express neural stem cell markers typical of resident multipotent vascular stem cells. Cell Tissue Res 358, 203–216 (2014). https://doi.org/10.1007/s00441-014-1937-2

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  • DOI: https://doi.org/10.1007/s00441-014-1937-2

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