Morpho-Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells after Activation or Inhibition of Epidermal Growth Factor and Toll-Like Receptors or Treatment with DNA Intercalator Cisplatin

Cytometry A. 2019 Jan;95(1):24-33. doi: 10.1002/cyto.a.23593. Epub 2018 Sep 21.

Abstract

This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control. At the same time, the cell population with a higher nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic signs of the regenerative potential increase. In other experiments, Herceptin was shown to suppress only the stemness signs of MSCs, while Cisplatin seriously affected cell viability in general, reducing synthetic and proliferative activities and causing cell morphology disturbances. © 2018 International Society for Advancement of Cytometry.

Keywords: Cisplatin; Herceptin; Toll-like receptor; c-Myc; epidermal growth factor; flow cytometry; immunocytochemistry; mesenchymal-epithelial transition; multipotent mesenchymal stromal cell; teichoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / chemistry
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cisplatin / pharmacology*
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / agonists
  • ErbB Receptors / antagonists & inhibitors
  • Flow Cytometry
  • Glycogen / metabolism
  • Glycosaminoglycans / biosynthesis
  • Glycosaminoglycans / metabolism
  • Humans
  • Intercalating Agents / pharmacology
  • Male
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Teichoic Acids / pharmacology
  • Toll-Like Receptors / metabolism
  • Trastuzumab / pharmacology

Substances

  • Glycosaminoglycans
  • Intercalating Agents
  • Proto-Oncogene Proteins c-myc
  • Teichoic Acids
  • Toll-Like Receptors
  • Epidermal Growth Factor
  • Glycogen
  • ErbB Receptors
  • Trastuzumab
  • Cisplatin