Influence of Microenvironmental Orchestration on Multicellular Lung Alveolar Organoid Development from Human Induced Pluripotent Stem Cells.

Autor:	Ozan VB; Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland., Wang H; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.; Department of Rheumatology and Immunology Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Akshay A; Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland.; Functional Urology Research Group, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Anand D; Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Hibaoui Y; Department of Gynecology and Obstetrics, Cantonal Hospital Fribourg, Fribourg, Switzerland., Feki A; Department of Gynecology and Obstetrics, Cantonal Hospital Fribourg, Fribourg, Switzerland., Gote-Schniering J; Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.; Department of Rheumatology and Immunology Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Gheinani AH; Functional Urology Research Group, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.; Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Heller M; Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Uldry AC; Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Lagache SB; Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Gazdhar A; Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Geiser T; Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. thomas.geiser@insel.ch.; Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland. thomas.geiser@insel.ch.
Jazyk:	angličtina
Zdroj:	Stem cell reviews and reports [Stem Cell Rev Rep] 2024 Oct 17. Date of Electronic Publication: 2024 Oct 17.
DOI:	10.1007/s12015-024-10789-1
Abstrakt:	Induced pluripotent stem cells (iPSCs) have emerged as promising in vitro tools, providing a robust system for disease modelling and facilitating drug screening. Human iPSCs have been successfully differentiated into lung cells and three-dimensional lung spheroids or organoids. The lung is a multicellular complex organ that develops under the symphonic influence of the microenvironment. Here, we hypothesize that the generation of lung organoids in a controlled microenvironment (cmO) (oxygen and pressure) yields multicellular organoids with architectural complexity resembling the lung alveoli. iPSCs were differentiated into mature lung organoids following a stepwise protocol in an oxygen and pressure-controlled microenvironment. The organoids developed in the controlled microenvironment displayed complex alveolar architecture and stained for SFTPC, PDPN, and KRT5, indicating the presence of alveolar epithelial type II and type I cells, as well as basal cells. Moreover, gene and protein expression levels were also increased in the cmO. Furthermore, pathway analysis of proteomics revealed upregulation of lung development-specific pathways in the cmO compared to those growing in normal culture conditions. In summary, by using a controlled microenvironment, we established a complex multicellular lung organoid derived from iPSCs as a novel cellular model to study lung alveolar biology in both lung health and disease. (© 2024. The Author(s).)
Databáze:	MEDLINE
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