Development of Human Lung Induction Models for Air Pollutants’ Toxicity Assessment

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-SiO2, 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-SiO2, and interference with surfactant secretion
in ATLs exposed to benzo­(a)­pyrene/nano-SiO2. 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.