Functioning human lung organoids model pulmonary tissue response from carbon nanomaterial exposures

Abstract

Human lung organoids (HLOs) are increasingly used to model development and infectious diseases, however their ability to recapitulate functional pulmonary tissue response to nanomaterials (NMs) has yet to be demonstrated. Here, we established a lung organoid exposure model that utilises microinjection to present NMs into the lumen of organoids. Our model assures efficient, reproducible and controllable exposure of the apical pulmonary epithelium, emulating real-life human exposure scenario. By comparing the impact of two well studied carbon-based NMs, graphene oxide sheets (GO) and multi-walled carbon nanotubes (MWCNT), we validated lung organoids as tools for predicting pulmonary NM-driven responses. In agreement with established in vivo data, we demonstrate that MWCNT, but not GO, elicit adverse effects on lung organoids, leading to a pro-fibrotic phenotype. Our findings reveal the capacity and suitability of HLOs for hazard assessment of NMs, aligned with the much sought-out 3Rs (animal research replacement, reduction, refinement) framework.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

“…This is in agreement with the results recently obtained after exposing human lung organoids (HLO) derived from embryonic stem cells to GO with different lateral dimensions. 294 The HLO contained six major epithelial cell types found in the lungs and were functional in terms of expressing beating cilia and secreting mucus and surfactants. The vast majority of GO sheets (regardless of their size) remained trapped in the mucus/surfactant and there was no or very limited uptake of the materials by the cells 7 days after microinjection of the materials directly inside the lumen of the organoids.…”

“…However, most of the material was trapped in the mucus and did not reach the cells. This is in agreement with the results recently obtained after exposing human lung organoids (HLO) derived from embryonic stem cells to GO with different lateral dimensions . The HLO contained six major epithelial cell types found in the lungs and were functional in terms of expressing beating cilia and secreting mucus and surfactants.…”