Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
권호 표지
DOI QR코드

DOI QR Code

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
Download PDF
⟨ Previous Next ⟩

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.

References

  1. Heo HR, Hong SH (2021) Generation of macrophage containing alveolar organoids derived from human pluripotent stem cells for pulmonary fibrosis modeling and drug efficacy testing. Cell Biosci 11:216.
  2. Heo HR, Kim J, Kim WJ, Yang SR, Han SS, Lee SJ, Hong Y, Hong SH (2019) Human pluripotent stem cell-derived alveolar epithelial cells are alternatives for in vitro pulmotoxicity assessment. Sci Rep 9:505.
  3. Heo JH, Kang D, Seo SJ, Jin Y (2022) Engineering the extracellular matrix for organoid culture. Int J Stem Cells 15:60-69. https://doi.org/10.15283/ijsc21190
  4. Hong Y, Chan N, Begum AN (2019) Deriving neural cells from pluripotent stem cells for nanotoxicity testing. In: Zhang Q (eds), Nanotoxicity. Methods in Molecular Biology, Vol. 1894. Humana Press, New York, NY, pp 57-72.
  5. Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Muhlberger E, Kotton DN (2020) SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. Cell Stem Cell 27:962-973.E7. https://doi.org/10.1016/j.stem.2020.09.013
  6. Kim J, Koo BK, Clevers H (2022) Organoid studies in COVID-19 research. Int J Stem Cells 15:3-13. https://doi.org/10.15283/ijsc21251
  7. Kim JH, An GH, Kim JY, Rasaei R, Kim WJ, Jin X, Woo DH, Han C, Yang SR, Kim JH, Hong SH (2021) Human pluripotent stem cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing. Cell Death Discov 7:48.
  8. Kim JH, Kim J, Kim WJ, Choi YH, Yang SR, Hong SH (2020) Diesel particulate matter 2.5 induces epithelial-to-mesenchymal transition and upregulation of SARS-CoV-2 receptor during human pluripotent stem cell-derived alveolar organoid development. Int J Environ Res Public Health 17:8410.
  9. Kook MG, Lee SE, Shin N, Kong D, Kim DH, Kim MS, Kang HK, Choi SW, Kang KS (2022) Generation of cortical brain organoid with vascularization by assembling with vascular spheroid. Int J Stem Cells 15:85-94. https://doi.org/10.15283/ijsc21157
  10. Kwon O, Yu WD, Son YS, Jung KB, Lee H, Son MY (2022) Generation of highly expandable intestinal spheroids composed of stem cells. Int J Stem Cells 15:104-111. https://doi.org/10.15283/ijsc21209
  11. Lee H, Lee J, Hong SH, Rahman I, Yang SR (2018) Inhibition of RAGE attenuates cigarette smoke-induced lung epithelial cell damage via RAGE-mediated Nrf2/DAMP signaling. Front Pharmacol 9:684.
  12. Lee H, Son MY (2021) Current challenges associated with the use of human induced pluripotent stem cell-derived organoids in regenerative medicine. Int J Stem Cells 14:9-20. https://doi.org/10.15283/ijsc20140
  13. Lee J, Kim JH, Hong SH, Yang SR (2021) Organoid model in idiopathic pulmonary fibrosis. Int J Stem Cells 14:1-8. https://doi.org/10.15283/ijsc20093
  14. Rajamani U, Gross AR, Ocampo C, Andres AM, Gottlieb RA, Sareen D (2017) Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives. Nat Commun 8:219.
  15. Suezawa T, Kanagaki S, Moriguchi K, Masui A, Nakao K, Toyomoto M, Tamai K, Mikawa R, Hirai T, Murakami K, Hagiwara M, Gotoh S (2021) Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids. Stem Cell Rep 16:2973-2987. https://doi.org/10.1016/j.stemcr.2021.10.015
  16. Tang L, Su J, Liang P (2017) Modeling cadmium-induced endothelial toxicity using human pluripotent stem cell-derived endothelial cells. Sci Rep 7:14811.
  17. Vanova T, Raska J, Babica P, Sovadinova I, Kunova Bosakova M, Dvorak P, Blaha L, Rotrekl V (2019) Freshwater cyanotoxin cylindrospermopsin has detrimental stage-specific effects on hepatic differentiation from human embryonic stem cells. Toxicol Sci 168:241-251. https://doi.org/10.1093/toxsci/kfy293