Perspectives of future lung toxicology studies using human pluripotent stem cells.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0417615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0738 (Electronic) Linking ISSN: 03405761 NLM ISO Abbreviation: Arch Toxicol Subsets: MEDLINE

Original Publication: Berlin, New York, Springer-Verlag.

Lung/*cytology ; Pluripotent Stem Cells/*cytology ; Toxicology/*methods; Animals ; Cell Culture Techniques ; Drug Evaluation, Preclinical/methods ; Drug Evaluation, Preclinical/trends ; Humans ; Lab-On-A-Chip Devices ; Organoids/cytology ; Toxicology/trends

The absence of in vitro platforms for human pulmonary toxicology studies is becoming an increasingly serious concern. The respiratory system has a dynamic mechanical structure that extends from the airways to the alveolar region. In addition, the epithelial, endothelial, stromal, and immune cells are highly organized in each region and interact with each other to function synergistically. These cells of varied lineage, particularly epithelial cells, have been difficult to use for long-term culture in vitro, thus limiting the development of useful experimental tools. This limitation has set a large distance between the bench and the bedside for analyzing the pathogenic mechanisms, the efficacy of candidate therapeutic agents, and the toxicity of compounds. Several researchers have proposed solutions to these problems by reporting on methods for generating human lung epithelial cells derived from pluripotent stem cells (PSCs). Moreover, the use of organoid culture, organ-on-a-chip, and material-based techniques have enabled the maintenance of functional PSC-derived lung epithelial cells as well as primary cells. The aforementioned technological advances have facilitated the in vitro recapitulation of genetic lung diseases and the detection of ameliorating or worsening effects of genetic and chemical interventions, thus indicating the future possibility of more sophisticated preclinical compound assessments in vitro. In this review, we will update the recent advances in lung cell culture methods, principally focusing on human PSC-derived lung epithelial organoid culture systems with the hope of their future application in toxicology studies.
(© 2021. The Author(s).)

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Keywords: Airway; Alveolar; Lung; Organoid; Pluripotent stem cell; iPS cell

Date Created: 20220101 Date Completed: 20220328 Latest Revision: 20220328

20221213

PMC8720162

10.1007/s00204-021-03188-9

34973109