State of the art on lung organoids in mammals

Abstract

The number and severity of diseases affecting lung development and adult respiratory function have stimulated great interest in developing new in vitro models to study lung in different species. Recent breakthroughs in 3-dimensional (3D) organoid cultures have led to new physiological in vitro models that better mimic the lung than conventional 2D cultures. Lung organoids simulate multiple aspects of the real organ, making them promising and useful models for studying organ development, function and disease (infection, cancer, genetic disease). Due to their dynamics in culture, they can serve as a sustainable source of functional cells (biobanking) and be manipulated genetically. Given the differences between species regarding developmental kinetics, the maturation of the lung at birth, the distribution of the different cell populations along the respiratory tract and species barriers for infectious diseases, there is a need for species-specific lung models capable of mimicking mammal lungs as they are of great interest for animal health and production, following the One Health approach. This paper reviews the latest developments in the growing field of lung organoids.

Human organoids in basic research and clinical applications

“…Lung has an extraordinary ability to regenerate and to restore its function after injury, which makes it possible to overcome the complexity and tedious procedure of differentiation from PSCs and generate lung-like tissues directly from AdSCs. 122 The airway contains basal stem cells that act as progenitors for self-renewal and secretory club cells that act as progenitors by showing plasticity after injury, while the alveolar epithelium has AECIIs to replenish lost AECIIs and produce AECIs after injury by proliferation. 123 – 126 Based on the regenerative capacity of lung cells, many groups have generated organoids from mouse and human airway basal cells, 123 , 127 , 128 airway secretory club cells 124 , 129 , 130 and AECIIs.…”

Regenerative medicine in lung diseases: A systematic review

“…Generating lungs in vitro and mimicking their function is a major challenge that requires a high degree of cell specialization and complex tissue architecture ( 5 , 48 , 70 , 71 ). They must provide a variety of organ functions, such as the diversity of airway cell types, the defense mechanisms that protect the upper airways (e.g., secretion of specifically composed mucus and active ciliary apparatus), and the coupling of the alveolar space with the surrounding systemic and pulmonary vasculature to ensure effective tissue perfusion and gas exchange ( 72 ).…”

“…Airway anatomy and physiology are highly species-dependent, making it necessary to create species-specific models. In a recent review of mammalian lung organoids, Archer et al ( 72 ) highlighted that the cells lining the bronchiolar or more distal part of the tracheobronchial tree differ considerably between species in terms of their abundance, the cell types present, the ultrastructural features of these cells in adult animals, and the secretory products they produce ( 72 ). Mouse models, for example, are not particularly well suited for studying human respiratory diseases.…”

“…On the other hand, sheep lungs are most commonly used as models for human lungs because of their anatomy and the uniform distribution of differentiated cells at a given age of maturity. These elements make sheep a valuable model for human respiratory physiology and disease ( 72 ).…”

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

“…The organoid also depicted a lung analogous transcriptional as well as functional profile. The lung organoid has already been proved valuable in regenerative medicine and lung disease modeling along with drug efficacy as well as toxicity analyses ( Dye et al, 2015 ; Chen et al, 2017 ; McCauley et al, 2017 ; Tan et al, 2017 ; Zacharias et al, 2018 ; Archer et al, 2021 ). For instance, syncytial virus tropism on the respiratory system has been explored using the lung organoid model ( Collins et al, 2013 ; Liesman et al, 2014 ; Chen et al, 2017 ).…”