Alteration of mesenchymal stem cells polarity by laminar shear stimulation promoting β-catenin nuclear localization

Biomaterials. 2019 Jan;190-191:1-10. doi: 10.1016/j.biomaterials.2018.10.026. Epub 2018 Oct 23.

Abstract

Mesenchymal stem cell (MSC) is mechanosensitive and the respond to mechanical force is pattern specific. We previously reported that oscillatory shear stress at 0.5 ± 4 dyne/cm2 guided MSCs polarity vertical to net flow direction before apolaric stage at 30 min resulting in phosphorylation of β-catenin and inhibition of Wnt signaling. This time, we explored laminar shear stress (LS) at 0.5 dyne/cm2 polarized MSCs by guiding F-actin orientation parallel to the flow direction before apolarity at 30 min accompanied with activation of Wnt signaling. Time-dependent microarray analysis supported cell-cell junctional complex of MSCs was the major mechanosensor on MSCs to respond 0.5 dyne/cm2 LS. Three-dimensional immunofluorescence image confirmed LS promoting β-catenin nuclear localization during 15 min to 1 h with a peak at 30 min. Functional analysis of proteomic study on MSC with 30 min LS stimulation indicated that upregulation of β-catenin downstream proteins related to cardiovascular development, endothelial cell protection and angiogenesis. Conditioned medium from MSCs with 30 min LS stimulation improved the viability of human endothelial cells from oxidative damage. In conclusion, 0.5 dyne/cm2 LS on MSCs for 30 min guides MSCs lack of polarity and promotes β-catenin nuclear translocation favoring Wnt activation and paracrine cardiovascular support.

Keywords: Cardiovascular; Laminar shear; Mesenchymal stem cells; Wnt; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Actins / metabolism
  • Cell Nucleus / metabolism*
  • Cell Polarity
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Protein Interaction Maps
  • Stress, Mechanical
  • Wnt Signaling Pathway
  • beta Catenin / analysis
  • beta Catenin / metabolism*

Substances

  • Actins
  • CTNNB1 protein, human
  • beta Catenin