Organogenesis of adult lung in a dish: Differentiation, disease and therapy

Abstract

The remarkable regenerative capacity of the lung suggests that stem cells could be of therapeutic importance in diverse lung diseases; however, the successful exploitation of lung stem cell biology has long been hampered by our inability to maintain and expand adult lung stem cells while retaining their multi-lineage potential in vitro. Recently, advances in our understanding of stem cell niches and the role of key signalling modulators in controlling stem cell maintenance and differentiation have fuelled the development of new in vitro three-dimensional (3D) culture technologies that sustain the stem cell-driven formation of near-physiological, self-organizing structures called organoids. Here we review basic approaches to organoid model systems and highlight recent achievements in the generation of organoids from adult stem and progenitor cells of both the murine and human lungs. We evaluate current applications in studying cellular changes in proliferation, differentiation, plasticity, and cell polarity, and cellular and molecular crosstalk of epithelial cells with stroma. Advantages and limitations of organoids for clinical use are also discussed.

Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening

“…4b). Immunofluorescence (IF) showed that the organoids were composed of basal cells expressing p63 in the outer cell layer 25,28 , as well as mucin-secreting cells (goblet cells) expressing MUC1 28 and ciliated cells expressing acetylated-tubulin and Arl13b in the luminal cell layer 25,28 (Fig. 4c).…”

“…Organoid models for both tracheobronchial and alveolar tissue have been developed from adult stem cells or pluripotent stem cells 25–27 and shown to recapitulate the epithelial organisation of these two distinct tissue types in vitro 14,26,28 . As personalised models for lung cancer, in vitro tissue culture 29 or tumour spheroid culture 10,30 using a 3D culture system has been studied to predict response to anticancer therapy, but have limited growth or recapitulation of original tumour architecture 23 .…”

Human Pulmonary 3D Models For Translational Research

“…Innovative live cell labeling combined with the use of viral transduction systems for gene editing will allow for mechanistic analysis of such lung tissue models in the future . The rapid development of stem cell based technologies; decellularization procedures and tissue printing make the building of human‐lung related tissue pieces for use in basic science more realistic within the next years.…”

Microfluidic Live-Imaging technology to perform research activities in 3D models

“…Cells in 2D culture are not surrounded by ECM and therefore are different from the structure of an in vivo cell system, as they cannot: migrate, polarize, differentiate in response to [9]- [12]. Despite their proven value in biomedical research, 2D models cannot support differentiated and cell-specific functions in tissues or accurately predict in vivo tissue functions and drug and biological modulator activities [13]- [16]. These limitations have led to a growing interest in the development of more complex models, such as those that incorporate multiple cell types or involve cell modeling, and in three-dimensional (3D) models, which better represent the spatial and chemical complexity of living tissues [17]- [19].…”