In Vitro Models to Study Human Lung Development, Disease and Homeostasis

Abstract

The main function of the lung is to support gas exchange, and defects in lung development or diseases affecting the structure and function of the lung can have fatal consequences. Most of what we currently understand about human lung development and disease has come from animal models. However, animal models are not always fully able to recapitulate human lung development and disease, highlighting an area where in vitro models of the human lung can compliment animal models to further understanding of critical developmental and pathological mechanisms. This review will discuss current advances in generating in vitro human lung models using primary human tissue, cell lines, and human pluripotent stem cell derived lung tissue, and will discuss crucial next steps in the field.

FIGURE 1.

Development and anatomy of the human lung Left: branching morphogenesis occurs during the pseudoglandular stage of lung development. At this time point, the proximal epithelial regions contain Sox2+ progenitor cells, whereas distal epithelial bud tips contain Sox9+ progenitors. As development progresses, Sox9+ distal bud tip progenitors give rise to alveolar-specific progenitor cells, and rudimentary saccules form (middle). Additionally, the proximal airway begins to form mature ciliated and secretory cells at this time. As the lung matures, saccules become mature alveolar structures comprised of AECI and AECII cells (right).

FIGURE 2.

In vitro models of the human lung A variety of in vitro human model systems have been developed using primary lung tissue (examples denoted in black text), lung cells from immortalized human cell lines (examples denoted in blue text), and lung-specific cells derived from hPSCs (examples denoted in pink text). These systems have been developed in a variety of contexts, including monolayer, ALI, or a variety of 3D and engineered environments to recapitulate elements of the native human lung.