@article{Bluhmki2021-08-23Funct-54772,
  year={2021},
  doi={10.1038/s41598-021-96565-4},
  title={Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96‑Transwell air-liquid interface model},
  number={1},
  volume={11},
  journal={Scientific Reports},
  author={Bluhmki, Teresa and Traub, Stefanie and Müller, Ann-Kathrin and Bitzer, Sarah and Schruf, Eva and Bammert, Marie-Therese and Leist, Marcel and Gantner, Florian and Garnett, James P. and Heilker, Ralf},
  note={Article Number: 17028}
}

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    <dc:creator>Traub, Stefanie</dc:creator>
    <dc:creator>Gantner, Florian</dc:creator>
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    <dcterms:abstract xml:lang="eng">In order to circumvent the limited access and donor variability of human primary alveolar cells, directed differentiation of human pluripotent stem cells (hiPSCs) into alveolar-like cells, provides a promising tool for respiratory disease modeling and drug discovery assays. In this work, a unique, miniaturized 96-Transwell microplate system is described where hiPSC-derived alveolar-like cells were cultured at an air-liquid interface (ALI). To this end, hiPSCs were differentiated into lung epithelial progenitor cells (LPCs) and subsequently matured into a functional alveolar type 2 (AT2)-like epithelium with monolayer-like morphology. AT2-like cells cultured at the physiological ALI conditions displayed characteristics of AT2 cells with classical alveolar surfactant protein expressions and lamellar-body like structures. The integrity of the epithelial barriers between the AT2-like cells was confirmed by applying a custom-made device for 96-parallelized transepithelial electric resistance (TEER) measurements. In order to generate an IPF disease-like phenotype in vitro, the functional AT2-like cells were stimulated with cytokines and growth factors present in the alveolar tissue of IPF patients. The cytokines stimulated the secretion of pro-fibrotic biomarker proteins both on the mRNA (messenger ribonucleic acid) and protein level. Thus, the hiPSC-derived and cellular model system enables the recapitulation of certain IPF hallmarks, while paving the route towards a miniaturized medium throughput approach of pharmaceutical drug discovery.</dcterms:abstract>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-09-02T06:43:47Z</dc:date>
    <dc:contributor>Traub, Stefanie</dc:contributor>
    <dc:contributor>Heilker, Ralf</dc:contributor>
    <dc:creator>Bluhmki, Teresa</dc:creator>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dc:contributor>Schruf, Eva</dc:contributor>
    <dc:creator>Leist, Marcel</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-09-02T06:43:47Z</dcterms:available>
    <dc:creator>Garnett, James P.</dc:creator>
    <dc:creator>Bitzer, Sarah</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/54772"/>
    <dc:creator>Schruf, Eva</dc:creator>
    <dc:creator>Bammert, Marie-Therese</dc:creator>
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    <dc:contributor>Garnett, James P.</dc:contributor>
    <dcterms:issued>2021-08-23</dcterms:issued>
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    <dcterms:title>Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96‑Transwell air-liquid interface model</dcterms:title>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:creator>Müller, Ann-Kathrin</dc:creator>
    <dc:creator>Heilker, Ralf</dc:creator>
    <dc:contributor>Müller, Ann-Kathrin</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:contributor>Bammert, Marie-Therese</dc:contributor>
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    <dc:language>eng</dc:language>
    <dc:contributor>Bluhmki, Teresa</dc:contributor>
    <dc:contributor>Bitzer, Sarah</dc:contributor>
    <dc:contributor>Gantner, Florian</dc:contributor>
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