Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene

Yingyan Zhou, Cun Li, Yanyan Chen, Yifei Yu, Xin Diao, Raymond Chiu, Jiacheng Fang, Yuting Shen, Jianing Wang, Lin Zhu*, Jie Zhou*, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.

Original languageEnglish
Pages (from-to)6083–6092
Number of pages10
JournalEnvironmental Science and Technology
Volume58
Issue number14
Early online date28 Mar 2024
DOIs
Publication statusPublished - 9 Apr 2024

Scopus Subject Areas

  • Chemistry(all)
  • Environmental Chemistry

User-Defined Keywords

  • 1-NP
  • MALDI-MSI
  • adult stem cell
  • human airway organoids
  • multimodal imaging analysis

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