학술논문
Pulmonary fibrosis model using micro-CT analyzable human PSC–derived alveolar organoids containing alveolar macrophage-like cells
Document Type
Original Paper
Author
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
Source
Cell Biology and Toxicology: An International Journal Devoted to Research at the Cellular Level. 38(4):557-575
Subject
Language
English
ISSN
0742-2091
1573-6822
1573-6822
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 (AMφ)–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 AMφ-specific markers. Furthermore, CD68+ AMφ-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.Graphical abstract: