A novel human 3D lung microtissue model for nanoparticle-induced cell-matrix alterations

Area of Science:

• Nanotoxicology
• In vitro toxicology
• Pulmonary toxicology

Background:

• Multi-walled carbon nanotubes (MWCNT) induce lung inflammation and fibrosis, but current in vivo testing is low-throughput.
• Existing 2D in vitro assays show conflicting results compared to in vivo nanoparticle toxicity studies.
• Three-dimensional (3D) in vitro models better mimic human physiology for toxicity testing.

Purpose of the Study:

• To evaluate the utility of scaffold-free 3D human lung microtissues for assessing chronic pulmonary toxicity.
• To compare the predictive capacity of 3D microtissues against traditional methods for nanoparticle and asbestos toxicity.
• To establish a more physiologically relevant in vitro model for nanomaterial safety assessment.

Main Methods:

• Co-culture of human lung fibroblasts, epithelial cells, and macrophages to create 3D lung microtissues.
• Exposure of microtissues to multi-walled carbon nanotubes (MWCNT), carbon black nanoparticles, or asbestos fibers.
• Assessment of microtissue viability, morphology, and gene/protein expression related to inflammation and extracellular matrix remodeling.

Main Results:

• 3D lung microtissues successfully incorporated tested nanomaterials and asbestos fibers.
• Differential gene expression linked to inflammation and extracellular matrix remodeling was observed.
• The study demonstrated the utility of 3D microtissues in predicting chronic pulmonary effects of MWCNT and asbestos.

Conclusions:

• 3D lung microtissues serve as a predictive in vitro platform for nanomaterial toxicity.
• This model facilitates assessment of cell-matrix alterations and toxicity pathways.
• 3D microtissues offer a more relevant and efficient approach for nanoparticle toxicity testing.