State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road, Beijing 100085, China.
College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Environ Sci Technol. 2021 Feb 16;55(4):2440-2451. doi: 10.1021/acs.est.0c05700. Epub 2021 Feb 4.
There is an urgent need for reliable and effective models to study air pollution health effects on human lungs. Here, we report the utilization of human pluripotent stem cell (hPSC) induction models for human lung progenitor cells (hLPs) and alveolar type 2 epithelial cell-like cells (ATLs) for the toxicity assessment of benzo(a)pyrene, nano-carbon black, and nano-SiO, as common air pollutants. We induced hPSCs to generate ATLs, which recapitulated key features of human lung type 2 alveolar epithelial cells, and tested the induction models for cellular uptake of nanoparticles and toxicity evaluations. Our findings reveal internalization of nano-carbon black, dose-dependent uptake of nano-SiO, and interference with surfactant secretion in ATLs exposed to benzo(a)pyrene/nano-SiO. Thus, hLP and ATL induction models could facilitate the evaluation of environmental pollutants potentially affecting the lungs. In conclusion, this is one of the first studies that managed to adopt hPSC pulmonary induction models in toxicology studies.
迫切需要可靠和有效的模型来研究空气污染对人类肺部的健康影响。在这里，我们报告了利用人类多能干细胞（hPSC）诱导模型生成人类肺祖细胞（hLPs）和肺泡 II 型上皮细胞样细胞（ATLs），以评估苯并[a]芘、纳米碳黑和纳米 SiO2 等常见空气污染物的毒性。我们诱导 hPSCs 生成 ATLs，这些细胞 recapitulated 人类肺 II 型肺泡上皮细胞的关键特征，并测试了细胞对纳米颗粒的摄取和毒性评估的诱导模型。我们的研究结果表明，纳米碳黑被内化，纳米 SiO2 呈剂量依赖性摄取，并且暴露于苯并[a]芘/纳米 SiO2 的 ATLs 中表面活性剂分泌受到干扰。因此，hLP 和 ATL 诱导模型可以促进对潜在影响肺部的环境污染物的评估。总之，这是首次成功将 hPSC 肺诱导模型应用于毒理学研究的研究之一。
