Preterminfants frequently suffer frompulmonary complications due to a physiological and
structural lung immaturity resulting in significant morbidity and mortality. Novel in vitro and
in vivo models are required to study the underlying mechanisms of late lung maturation
and to facilitate the development of new therapeutic strategies. Organoids recapitulate
essential aspects of structural organization and possibly organ function, and can be
used to model developmental and disease processes. We aimed at generating fetal
lung organoids (LOs) and to functionally characterize this in vitro model in comparison
to primary lung epithelial cells and lung explants ex vivo. LOs were generated with
alveolar and endothelial cells from fetal rat lung tissue, using a Matrigel-gradient and
air-liquid-interface culture conditions. Immunocytochemical analysis showed that the LOs
consisted of polarized epithelial cell adhesion molecule (EpCAM)-positive cells with the
apical membrane compartment facing the organoid lumen. Expression of the alveolar
type 2 cell marker, RT2-70, and the Club cell marker, CC-10, were observed. Na+
transporter and surfactant protein mRNA expression were detected in the LOs. First
time patch clamp analyses demonstrated the presence of several ion channels with
specific electrophysiological properties, comparable to vital lung slices. Furthermore, the
responsiveness of LOs to glucocorticoids was demonstrated. Finally, maturation of LOs
induced by mesenchymal stem cells confirmed the convenience of the model to test and
establish novel therapeutic strategies. The results showed that fetal LOs replicate key
biological lung functions essential for lung maturation and therefore constitute a suitable
in vitro model system to study lung development and related diseases.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84315 |
| Date | 24 March 2023 |
| Creators | Laube, Mandy, Pietsch, Soeren, Pannicke, Thomas, Thome, Ulrich H., Fabian, Claire |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2296-858X, 678438 |
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