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Human Pluripotent Stem Cell-Derived Alveolar Epithelial Cells as a Tool to Assess Cytotoxicity of Particulate Matter and Cigarette Smoke Extract

  • Jung-Hyun Kim (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Minje Kang (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Ji-Hye Jung (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Seung-Joon Lee (Department of Internal Medicine, School of Medicine, Kangwon National University) ;
  • Seok-Ho Hong (Department of Internal Medicine, School of Medicine, Kangwon National University)
  • Received : 2022.10.02
  • Accepted : 2022.12.16
  • Published : 2022.12.31

Abstract

Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-β, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 ㎍/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.

Keywords

Acknowledgement

This research was supported by "Regional Innovation Strategy (RIS)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE)(2022RIS-005) and in part by the "Experts Training Graduate Program for Particulate Matter Management", a program of the Ministry of the Environment, Korea.

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