Human Pluripotent Stem Cell-Derived Alveolar Epithelial Cells as a Tool to Assess Cytotoxicity of Particulate Matter and Cigarette Smoke Extract
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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 μg/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.
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 μg/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.
참고문헌 (17)
- Heo HR, "Generation of macrophage containing alveolar organoids derived from human pluripotent stem cells for pulmonary fibrosis modeling and drug efficacy testing", Cell Biosci, 11, pp.216~ (2021)
- Heo HR, "Human pluripotent stem cell-derived alveolar epithelial cells are alternatives for in vitro pulmotoxicity assessment", Sci Rep, 9, pp.505~ (2019)
- Heo JH, "Engineering the extracellular matrix for organoid culture", Int J Stem Cells, 15, pp.60~69 (2022)
- Hong Y, "Nanotoxicity. Methods in Molecular Biology, Vol. 1894", pp.57~72 (2019), Humana Press
- Huang J, "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, pp.962~973 (2020)[DOI]
- Kim J, "Organoid studies in COVID-19 research", Int J Stem Cells, 15, pp.3~13 (2022)
- Kim JH, "Human pluripotent stem cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing", Cell Death Discov, 7, pp.48~ (2021)
- Kim JH, "Diesel particulate matter 2.5induces 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, pp.8410~ (2020)
- Kook MG, "Generation of cortical brain organoid with vascularization by assembling with vascular spheroid", Int J Stem Cells, 15, pp.85~94 (2022)
- Kwon O, "Generation of highly expandable intestinal spheroids composed of stem cells", Int J Stem Cells, 15, pp.104~111 (2022)
- Lee H, "Inhibition of RAGE attenuates cigarette smoke-induced lung epithelial cell damage via RAGE-mediated Nrf2", DAMP signaling, 2018, pp.9, 684~
- Lee H, "Current challenges associated with the use of human induced pluripotent stem cell-derived organoids in regenerative medicine", Int J Stem Cells, 14, pp.9~20 (2021)
- Lee J, "Organoid model in idiopathic pulmonary fibrosis", Int J Stem Cells, 14, pp.1~8 (2021)
- Rajamani U, "Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives", Nat Commun, 8, pp.219~ (2017)
- Suezawa T, "Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids", Stem Cell Rep, 16, pp.2973~2987 (2021)
- Tang L, "Modeling cadmium-induced endothelial toxicity using human pluripotent stem cell-derived endothelial cells", Sci Rep, 7, pp.14811~ (2017)
- Vanova T, "Freshwater cyanotoxin cylindrospermopsin has detrimental stage-specific effects on hepatic differentiation from human embryonic stem cells", Toxicol Sci, 168, pp.241~251 (2019)