Respiratory Toxicity

The respiratory system is a target of toxic effects, and is also a major route of absorption of inhaled substances and atmospheric particles. Thus, respiratory toxicity is an active area of research in drug development and discovery, as well as in environmental studies. Cellular responses to toxicants lead to acute effects such as inflammation or chronic effects including fibrosis, emphysema, and cancer. It is crucial to develop methods that will detect potential respiratory toxicity as early and quickly as possible. Researchers use monocellular cultures to more complex multicellular systems. These models are tools to better study lung physiology, tissue infection and inflammation, as well as serving as a platform for identification of novel targets and screening of candidate drugs for lung disorders and potential respiratory toxicity.

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Novel Co-Culture Model

Novel Co-Culture Model to Demonstrate the Inflammatory Effects of Respiratory Infection on Healthy Human Airway Cells.

The standard Lonza B-ALI™ System was utilized to produce the viable NHBE membranes from 3 different donors.

In this study, we developed and optimized a co-culture model where immune cells (Peripheral Blood Mononuclear Cells, PBMCs) are co-cultured alongside lung cells (Normal Human Bronchial Epithelial Cells, NHBEs) using Lonza’s B-ALI™ (Bronchial Air-Liquid Interface) System. We show that our optimized model supports functional epithelial membranes on the air interface, while the immune cell population remained stable and active. We then validated this co-culture as a physiologically-relevant model for viral induced inflammation by stimulating the T cell population with viral antigens.

Airway Cells from Lonza

Lonza offers a comprehensive range of normal human primary airway cells with broad donor variety for bronchial epithelial cells, bronchial smooth muscle cells, lung fibroblasts, pulmonary artery endothelial cells, pulmonary artery smooth muscle cells, small-airway/alveolar epithelial cells and lung microvascular endothelial cells. These cells can be used to build robust models for respiratory toxicity studies as mono-cultures or organotypic co-culture models.

Cell Type	Source	Recommended BulletKit® Media	Additional Information
Bronchial Epithelial Cell (NHBE)	Epithelial lining of airways above bifurcation of lungs	BEGM® BulletKit® Medium or B-ALI BulletKit® Medium	Certain batches are screened for suitability in air-liquid interface (ALI) studies and are guaranteed for differentiation marked by cilia formation, mucin production, and TEER levels
Bronchial Smooth Muscle Cells (BSMC)	Major bronchia	SmGM®-2 BulletKit® Medium
Lung Endothelial Cells (HMVEC-L)	Small vessels within lung tissue	EGM®-2 BulletKit® Medium	HMVEC-L are cultured to be >90% pure with a mixture of lymphatic endothelial cells (LEC) and blood endothelial cells (BEC). All batches are screened for and reported with % LEC and %BEC.
Lung Fibroblasts	Lung tissue	FGM®-2 BulletKit® Medium
Pulmonary Artery Endothelial Cells	Pulmonary artery	EGM®-2 BulletKit® Medium
Pulmonary Artery Smooth Muscle Cells	Pulmonary artery	SmGM®-2 BulletKit® Medium
Small Airway Epithelial Cells	Distal portion of lung in the bronchiole area	SAGM™ BulletKit® Medium or S-ALI BulletKit® Medium	Certain batches are screened for suitability in air-liquid interface (ALI) studies and are guaranteed for differentiation marked by cilia formation, mucin production, and TEER levels