Human chorionic villous mesenchymal stem/stromal cells protect endothelial cells from injury induced by high level of glucose

Stem Cell Res Ther. 2018 Sep 21;9(1):238. doi: 10.1186/s13287-018-0984-0.

Abstract

Background: Mesenchymal stem/stromal cells derived from chorionic villi of human term placentae (pMSCs) protect human endothelial cells from injury induced by hydrogen peroxide (H2O2). In diabetes, elevated levels of glucose (hyperglycaemia) induce H2O2 production, which causes the endothelial dysfunction that underlies the enhanced immune responses and adverse complications associated with diabetes, which leads to thrombosis and atherosclerosis. In this study, we examined the ability of pMSCs to protect endothelial cell functions from the negative impact of high level of glucose.

Methods: pMSCs isolated from the chorionic villi of human term placentae were cultured with endothelial cells isolated from human umbilical cord veins in the presence of glucose. Endothelial cell functions were then determined. The effect of pMSCs on gene expression in glucose-treated endothelial cells was also determined.

Results: pMSCs reversed the effect of glucose on key endothelial cell functions including proliferation, migration, angiogenesis, and permeability. In addition, pMSCs altered the expression of many genes that mediate important endothelial cell functions including survival, apoptosis, adhesion, permeability, and angiogenesis.

Conclusions: This is the first comprehensive study to provide evidence that pMSCs protect endothelial cells from glucose-induced damage. Therefore, pMSCs have potential therapeutic value as a stem cell-based therapy to repair glucose-induced vascular injury and prevent the adverse complications associated with diabetes and cardiovascular disease. However, further studies are necessary to reveal more detailed aspects of the mechanism of action of pMSCs on glucose-induced endothelial damage in vitro and in vivo.

Keywords: Chorionic villous mesenchymal stromal cells; Endothelial cells; Endothelium permeability; Gene expression; Glucose; Migration; Monocyte invasion; Placenta; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Membrane Permeability / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chorionic Villi / metabolism
  • Coculture Techniques
  • Collagen / chemistry
  • Collagen / genetics
  • Collagen / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Drug Combinations
  • Endothelins / genetics
  • Endothelins / metabolism
  • Female
  • Gene Expression Regulation / drug effects*
  • Glucose / antagonists & inhibitors
  • Glucose / pharmacology*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism
  • Laminin / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Pregnancy
  • Proteoglycans / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • THP-1 Cells
  • Umbilical Cord / cytology
  • Umbilical Cord / metabolism

Substances

  • Chemokines
  • Culture Media, Conditioned
  • Drug Combinations
  • Endothelins
  • Interleukins
  • Laminin
  • Membrane Glycoproteins
  • Proteoglycans
  • Receptors, Cell Surface
  • matrigel
  • Collagen
  • Glucose