Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches

Int J Environ Res Public Health. 2017 Apr 20;14(4):440. doi: 10.3390/ijerph14040440.

Abstract

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro at various concentrations (15 to 300 µg/mL) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased proliferation of BM-MSCs, while higher concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a concentration-dependent manner. The X-ray fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses demonstrated that heavy metals were associated with signaling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential expression of the apoptosis genes (BCL2, BAX); inflammation associated genes (TNF-α and IL-6) and the cell cycle regulation gene (p53). We conclude that PM causes inflammation and cell death, and thereby predisposes to chronic debilitating diseases.

Keywords: BM-MSCs; IPA; cell death; cell proliferation; particulate matter; qRT-PCR.

MeSH terms

  • Air Pollutants / toxicity*
  • Apoptosis / drug effects*
  • Bone Marrow Cells / drug effects*
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Middle Aged
  • Particle Size
  • Particulate Matter / toxicity*
  • Saudi Arabia
  • Signal Transduction / drug effects*

Substances

  • Air Pollutants
  • Particulate Matter