Impaired Communication through Gap Junctions Reduces the Angiogenic Potential of the Secretome in Mesenchymal Stromal Cell-Endothelial Cell Interactions In Vitro

Bull Exp Biol Med. 2024 Nov;178(1):139-144. doi: 10.1007/s10517-024-06296-5. Epub 2024 Nov 23.

Abstract

Highly specialized gap junctions play an important role in the interaction between endothelial (EC) and multipotent mesenchymal stromal cells (MSC). Inhibition of gap junctions with a specific inhibitor carbenoxolone attenuates the effects of the medium conditioned by MSC-EC co-culture on proliferation and migration of cultured EC. In conditioned medium from co-culture, the levels of angiogenic mediators (VEGF-A, FGF-2, MCP-1, etc.) were decreased, which apparently determines lower angiogenic effect of the conditioned medium on the growth of the vascular network in the chorioallantois membrane of quail embryo in ovo. Suppression of communication through gap junctions in associations of MSC and EC, the structural and functional units of physiological and reparative angiogenesis, can directly reduce the level of proangiogenic mediators in the microenvironment, which, in turn, can help to control the regulation of vascular function in pathologies.

Keywords: angiogenesis; endothelial cells; gap junctions; multipotent mesenchymal stromal cells; paracrine regulation.

MeSH terms

  • Animals
  • Carbenoxolone / pharmacology
  • Cell Communication* / drug effects
  • Cell Communication* / physiology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / metabolism
  • Coculture Techniques*
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Gap Junctions* / drug effects
  • Gap Junctions* / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • Neovascularization, Physiologic* / drug effects
  • Neovascularization, Physiologic* / physiology
  • Quail
  • Secretome / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Culture Media, Conditioned
  • Vascular Endothelial Growth Factor A
  • Carbenoxolone
  • Fibroblast Growth Factor 2
  • Chemokine CCL2