Evidence map›Paper›PMID 34426605›Full record

ArticleScientific reports2021

Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96‑Transwell air-liquid interface model.

Teresa Bluhmki, Stefanie Traub, Ann-Kathrin Müller, Sarah Bitzer, Eva Schruf, Marie-Therese Bammert, Marcel Leist, Florian Gantner, James P Garnett, Ralf Heilker

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Teresa BluhmkiDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany. teresa.bluhmki@boehringer-ingelheim.com.
Stefanie TraubTrenzyme GmbH, Byk-Gulden-Str. 2, 78467, Constance, Germany.
Ann-Kathrin MüllerTrenzyme GmbH, Byk-Gulden-Str. 2, 78467, Constance, Germany.
Sarah BitzerDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany.
Eva SchrufDepartment of Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany.
Marie-Therese BammertDepartment of Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany.
Marcel LeistIn-vitro Toxicology and Biomedicine, University of Konstanz, 78457, Constance, Germany.
Florian GantnerDepartment of Translational Medicine and Clinical Pharmacology, C. H. Boehringer Sohn AG & Co. KG, 88397, Biberach an der Riss, Germany.
James P GarnettDepartment of Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany.
Ralf HeilkerDepartment of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach an der Riss, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AirCell Culture TechniquesMiniaturizationModels, BiologicalBiomarkersCell DifferentiationCells, CulturedHumansInduced Pluripotent Stem CellsPhenotypePulmonary AlveoliPulmonary FibrosisTranscription, GeneticBiomarkers

Identifiers

PMID34426605
PMCPMC8382767

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.