Synergism of Biochemical and Mechanical Stimuli in the Differentiation of Human Placenta-Derived Multipotent Cells Into Endothelial Cells

J Biomech. 2008;41(4):813-21. doi: 10.1016/j.jbiomech.2007.11.008. Epub 2008 Jan 10.

Abstract

There have been intensive studies on the differentiation of endothelial progenitor cells (EPCs) into endothelial cells. We investigated the endothelial differentiation of placenta-derived multipotent cells (PDMCs), a population of CD34(-)/CD133(-)/Flk-1(-) cells. PDMCs were cultured in basal media or media containing endothelial growth factors (EGM), including vascular endothelial growth factor (VEGF), for 3 days and then subjected to shear stress of 6 or 12dyn/cm(2) for 24h. Culture of PDMCs in EGM under static conditions resulted in significant increases in VEGF receptor-1 (Flt-1) and receptor-2 (Flk-1) expression. Application of shear stress at 12dyn/cm(2) to these cells led to significant increases in their expression of von Willebrand Factor and platelet-endothelial cell adhesion molecule-1 at both the gene and protein levels. Shear stress at 6dyn/cm(2) had lesser effects. Uptakes of acetylated low-density lipoproteins as well as formation of tube-like structures on Matrigel were significantly increased after subjecting to shear stress of 12dyn/cm(2) for 24h. Our findings suggest that the combined use of endothelial growth factors and high shear stress is synergistic for the endothelial differentiation of PDMCs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Adhesion / physiology
  • Cell Differentiation / physiology*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / cytology*
  • Endothelial Cells / physiology
  • Female
  • Humans
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / physiology
  • Placenta / cytology*
  • Placenta / physiology
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
  • Platelet Endothelial Cell Adhesion Molecule-1 / physiology
  • Pregnancy
  • Shear Strength
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / physiology
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-1 / physiology
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-2 / physiology
  • von Willebrand Factor / biosynthesis
  • von Willebrand Factor / physiology

Substances

  • Culture Media, Conditioned
  • Platelet Endothelial Cell Adhesion Molecule-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2