Lung Organoids and Their Use To Study Cell-Cell Interaction

Abstract

Purpose of review: The lung research field has pioneered the use of organoids for the study of cell-cell interactions.

Recent findings: The use of organoids for airway basal cells is routine. However, the development of organoids for the other regions of the lung is still in its infancy. Such cultures usually rely on cell-cell interactions between the stem cells and a putative niche cell for their growth and differentiation.

Summary: The use of co-culture organoid systems has facilitated the in vitro cultivation of previously inaccessible stem cell populations, providing a novel method for dissecting the molecular requirements of these cell-cell interactions. Future technology development will allow the growth of epithelial-only organoids in more defined media and also the introduction of specific non-epithelial cells for the study of cell interactions. These developments will require an improved understanding of the epithelial and non-epithelial cell types present in the lung and their lineage relationships.

Keywords: Human lung; Lung progenitors; Mouse lung; Organoids; iPSCs.

Fig. 1

Cellular organisation of the human lung. The cellular complexity of the human lung epithelium. a Section through large human intra-lobar airway stained to show ciliated cell nuclei (FOXJ1⁺; green) and mucous-producing Goblet cells (SCGB1A1⁺; red). It should be noted that Goblet cells are less prominent than Ciliated cells. The third major airway epithelial cell type (Basal cells) is shown in green in the inset as TRP63⁺ cells (arrowheads). The green background (due to auto-fluorescence from the tissue) nicely illustrates the airway-associated mesenchyme which has yet to be extensively characterised. b Section through a smaller human airway also showing the adjacent alveolar region. Here, cilia are visualised using an acetylated-tubulin antibody (green). Goblet cells are not shown, but are found at similar frequency to a. Note that the airway-associated mesenchyme is less extensive than in that in a. Type II alveolar cells are visualised using pro-SFTPC staining (red). The mesenchyme in the alveolar region is even less extensive and tightly associated with the epithelium. Scale bars: a 100 μm; b 50 μm (inset)