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Cited by 48Pluripotent Stem Cells ResearchNeonatal Respiratory Health ResearchInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium

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Abo, Kristine M., Sainz de Aja, Julio, Lindstrom-Vautrin, Jonathan, Alysandratos, Konstantinos-Dionysios, Richards, Alexsia, Garcia-de-Alba, Carolina, Huang, Jessie, Hix, Olivia T. +9 more·2022·JCI Insight
DOI 10.1172/jci.insight.155589PMC PMC8986076
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Abstract

Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as useful tools to elucidate functional characteristics of AT2s in homeostasis and disease. We and others recently adapted human induced pluripotent stem cell–derived AT2s (iAT2s) for air-liquid interface (ALI) culture. Here, we comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. We find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. We then leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor.

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  • Previous studies reported enhanced maturation, development, and function of human organoids in the laboratory.

    “These previous studies have reported enhanced maturation, development, and function of human organoids in the laboratory [16, 28].”

    From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [28]

    The Results section reports greater maturation-marker expression in human iAT2 cells cultured at an air–liquid interface than in 3D spheres, and greater barrier function than in submerged 2D culture. The Discussion describes functional AT2 characteristics. However, the enhanced maturation and function were observed in air–liquid interface cultures, not in the 3D organoids themselves; the paper does not establish enhanced organoid development. (LLM, conf=0.86)

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References 49 · Cited by 48

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Authors
Abo, K. M., Sainz de Aja, J., Lindstrom-Vautrin, J., Alysandratos, K.-D., Richards, A., Garcia-de-Alba, C., Huang, J., Hix, O. T., Werder, R. B., Bullitt, E., Hinds, A., Falconer, I., Villacorta-Martin, C., Jaenisch, R., Kim, C. F., Kotton, D. N., & Wilson, A. A.
Affiliations
  • Boston University (US)
  • Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children’s Hospital, Boston, Massachusetts, USA.
  • Whitehead Institute for Biomedical Research (US)
  • Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts, USA.
  • Boston Children's Hospital (US)
Corresponding author
Wilson, Andrew A.
ORCID
Venue
JCI Insight
Publisher
American Society for Clinical Investigation
Published
2022-03-22
Volume
7
Issue
6
ISSN
2379-3708 (ISSN-L)
DOI
10.1172/jci.insight.155589
PMC
PMC8986076
OpenAlex
W4221112967
Cited by
48
References
49
Citations by year
2026: 11 · 2025: 14 · 2024: 9 · 2023: 9 · 2022: 5
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • JCI Insight (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
  • Pulmonary Fibrosis Foundation
  • Massachusetts Consortium on Pathogen Readiness
  • National Institutes of Health (U01TR001810, N01 75N92020C00005, 75N92020C00005)
  • National Heart, Lung, and Blood Institute (U01HL134745, U01HL134766, 75N92020C00005, U01HL148692, F30HL147426, R35HL150876, P01HL152953, R01HL095993)
  • National Institute of Allergy and Infectious Diseases (U19AI131135)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK117940, R01DK101501)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Keywords
air-liquid interface culture, alveolar type II cells, environmental exposure, cigarette smoke, electronic cigarette vapor, inhaled toxicants, gene expression profiling
MeSH terms
Environmental Exposure, Epithelium, Humans, Pluripotent Stem Cells, Induced Pluripotent Stem Cells, Electronic Nicotine Delivery Systems

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