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Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages
Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of hu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409017/ https://www.ncbi.nlm.nih.gov/pubmed/36012471 http://dx.doi.org/10.3390/ijms23169211 |
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author | Seo, Ha-Rim Han, Hyeong-Jun Lee, Youngsun Noh, Young-Woock Cho, Seung-Ju Kim, Jung-Hyun |
author_facet | Seo, Ha-Rim Han, Hyeong-Jun Lee, Youngsun Noh, Young-Woock Cho, Seung-Ju Kim, Jung-Hyun |
author_sort | Seo, Ha-Rim |
collection | PubMed |
description | Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of human AOs as models of inflammatory diseases. In this study, we generated AOs containing a functional macrophage derived from hPSCs based on human fetal lung development using biomimetic strategies. We optimized culture conditions to maintain the iMACs (induced hPSC-derived macrophages) AOs for up to 14 days. In lipopolysaccharide (LPS)-induced inflammatory conditions, IL-1β, MCP-1 and TNF-α levels were significantly increased in iMAC-AOs, which were not detected in AOs. In addition, chemotactic factor IL-8, which is produced by mononuclear phagocytic cells, was induced by LPS treatment in iMACs-AOs. iMACs-AOs can be used to understand pulmonary infectious diseases and is a useful tool in identifying the mechanism of action of therapeutic drugs in humans. Our study highlights the importance of immune cell presentation in AOs for modeling inflammatory pulmonary diseases. |
format | Online Article Text |
id | pubmed-9409017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94090172022-08-26 Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages Seo, Ha-Rim Han, Hyeong-Jun Lee, Youngsun Noh, Young-Woock Cho, Seung-Ju Kim, Jung-Hyun Int J Mol Sci Article Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of human AOs as models of inflammatory diseases. In this study, we generated AOs containing a functional macrophage derived from hPSCs based on human fetal lung development using biomimetic strategies. We optimized culture conditions to maintain the iMACs (induced hPSC-derived macrophages) AOs for up to 14 days. In lipopolysaccharide (LPS)-induced inflammatory conditions, IL-1β, MCP-1 and TNF-α levels were significantly increased in iMAC-AOs, which were not detected in AOs. In addition, chemotactic factor IL-8, which is produced by mononuclear phagocytic cells, was induced by LPS treatment in iMACs-AOs. iMACs-AOs can be used to understand pulmonary infectious diseases and is a useful tool in identifying the mechanism of action of therapeutic drugs in humans. Our study highlights the importance of immune cell presentation in AOs for modeling inflammatory pulmonary diseases. MDPI 2022-08-16 /pmc/articles/PMC9409017/ /pubmed/36012471 http://dx.doi.org/10.3390/ijms23169211 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seo, Ha-Rim Han, Hyeong-Jun Lee, Youngsun Noh, Young-Woock Cho, Seung-Ju Kim, Jung-Hyun Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title | Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title_full | Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title_fullStr | Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title_full_unstemmed | Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title_short | Human Pluripotent Stem Cell-Derived Alveolar Organoid with Macrophages |
title_sort | human pluripotent stem cell-derived alveolar organoid with macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409017/ https://www.ncbi.nlm.nih.gov/pubmed/36012471 http://dx.doi.org/10.3390/ijms23169211 |
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