Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity

  • Ji-Hye Jung (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Se-Ran Yang (Department of Thoracic and Cardiovascular Surgery, Kangwon National University School of Medicine) ;
  • Woo Jin Kim (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Chin Kook Rhee (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Seok-Ho Hong (Department of Internal Medicine, Kangwon National University School of Medicine)
  • Received : 2023.08.25
  • Accepted : 2023.11.22
  • Published : 2024.01.31
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Abstract

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

Keywords

Acknowledgement

This research was supported by a grant from the Korean Fund for Regenerative Medicine (KFRM) funded by the Korean government (the Ministry of Science and ICT, the Ministry of Health & Welfare) (22A0304L1-01) as well as the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2022M3A9E4016936). Finally, this study was funded in part by Particulate Matter Management Specialized Graduate Program through the Korea Environmental Industry & Technology Institute (KEITI) and the KEITI through the Core Technology Development Project for Environmental Disease Prevention and Management (Grant number 2022003310008) funded by the Ministry of Environment (MOE).

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