Human Pluripotent Stem Cell-Derived Alveolar Epithelial Cells as a Tool to Assess Cytotoxicity of Particulate Matter and Cigarette Smoke Extract.
Jung-Hyun KimMinje KangJi-Hye JungSeung-Joon LeeSeok-Ho HongPublished in: Development & reproduction (2022)
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.
Keyphrases
- particulate matter
- oxidative stress
- pluripotent stem cells
- air pollution
- diabetic rats
- cell death
- endothelial cells
- ischemia reperfusion injury
- dna damage
- induced apoptosis
- high glucose
- high throughput
- smoking cessation
- poor prognosis
- cell cycle arrest
- rheumatoid arthritis
- working memory
- genome wide
- heat shock
- gene expression
- dna methylation
- transcription factor
- human health
- cell proliferation
- polycyclic aromatic hydrocarbons
- drug induced
- heat shock protein