Human Lung Organoids-A Novel Experimental and Precision Medicine Approach

Abstract

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research. For acute infectious and chronic inflammatory diseases as well as lung cancer, human lung organoids have opened possibilities for precise in vitro research and a deeper understanding of mechanisms underlying lung injury and regeneration. Human lung organoids from induced pluripotent stem cells or from adult stem cells of patients' samples introduce tools for understanding developmental processes and personalized medicine approaches. When further state-of-the-art technologies and protocols come into use, the full potential of human lung organoids can be harnessed. High-throughput assays in drug development, gene therapy, and organoid transplantation are current applications of organoids in translational research. In this review, we emphasize novel approaches in translational and personalized medicine in lung research focusing on the use of human lung organoids.

Keywords: airways; disease models; lung epithelium; organoids; personalized medicine; translational research.

Figure 1

Cell components of the respiratory system. Airways are formed by a pseudostratified epithelium composed of diverse basal, ciliated, and secretory cells. The alveoli are lined by squamous alveolar type 1 cells and cuboidal alveolar type 2 cells (adapted from Barkauskas et al. [8]).

Figure 2

Diversity of currently available model systems for lung research.

Figure 3

Schematic visualization of human bronchiolar and alveolar lung organoids and their cellular composition (adapted from Barkauskas et al. [8]).

Figure 4

Lung organoids have a huge potential in translational and personalized medicine. Applications and future possible usages are depicted [81,83,93,94,118,122,124,128,134].