Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cellsopen access
- Authors
- Choi, Seri; Choi, Jiwoong; Cheon, Seongmin; Song, Jihong; Kim, Seung-Yeon; Kim, Ji-eun; Nam, Dae-Hwan; Manzar, Gohar; Kim, Su-Man; Kang, Hyung-Sik; Kim, Kee K.; Jeong, Sang Hoon; Lee, Ju-Han; Park, Eun-Kee; Lee, Minseob; Lee, Hyang-Ae; Kim, Ki-Suk; Park, Han-Jin; Oh, Won Keun; Park, Chungoo; Lee, Chang Hyun; Kim, Eun-Mi
- Issue Date
- 8월-2022
- Publisher
- SPRINGER
- Keywords
- Human alveolar organoid; Fibrosis model; Micro-CT; Alveolar macrophage
- Citation
- CELL BIOLOGY AND TOXICOLOGY, v.38, no.4, pp.557 - 575
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL BIOLOGY AND TOXICOLOGY
- Volume
- 38
- Number
- 4
- Start Page
- 557
- End Page
- 575
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/145860
- DOI
- 10.1007/s10565-022-09698-1
- ISSN
- 0742-2091
- Abstract
- Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AM phi)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AM phi-specific markers. Furthermore, CD68(+) AM phi-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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