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A Monoclonal Human Alveolar Epithelial Cell Line ("Arlo") with Pronounced Barrier Function for Studying Drug Permeability and Viral Infections.
Carius, Patrick; Jungmann, Annemarie; Bechtel, Marco; Grißmer, Alexander; Boese, Annette; Gasparoni, Gilles; Salhab, Abdulrahman; Seipelt, Ralf; Urbschat, Klaus; Richter, Clémentine; Meier, Carola; Bojkova, Denisa; Cinatl, Jindrich; Walter, Jörn; Schneider-Daum, Nicole; Lehr, Claus-Michael.
  • Carius P; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.
  • Jungmann A; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany.
  • Bechtel M; Department of Genetics and Epigenetics, Saarland University, Campus A2 4, 66123, Saarbrücken, Germany.
  • Grißmer A; Institute of Medical Virology, University Hospital Frankfurt, Paul-Ehrlich-Str. 40, 60596, Frankfurt am Main, Germany.
  • Boese A; Department of Anatomy and Cellular Biology, Saarland University, Kirrberger Straße, Building 61, 66421, Homburg Saar, Germany.
  • Gasparoni G; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.
  • Salhab A; Department of Genetics and Epigenetics, Saarland University, Campus A2 4, 66123, Saarbrücken, Germany.
  • Seipelt R; Department of Genetics and Epigenetics, Saarland University, Campus A2 4, 66123, Saarbrücken, Germany.
  • Urbschat K; Section of Thoracic Surgery of the Saar Lung Center, SHG Clinics Völklingen, Richardstraße 5-9, 66333, Völklingen, Germany.
  • Richter C; Section of Thoracic Surgery of the Saar Lung Center, SHG Clinics Völklingen, Richardstraße 5-9, 66333, Völklingen, Germany.
  • Meier C; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.
  • Bojkova D; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany.
  • Cinatl J; Department of Anatomy and Cellular Biology, Saarland University, Kirrberger Straße, Building 61, 66421, Homburg Saar, Germany.
  • Walter J; Institute of Medical Virology, University Hospital Frankfurt, Paul-Ehrlich-Str. 40, 60596, Frankfurt am Main, Germany.
  • Schneider-Daum N; Institute of Medical Virology, University Hospital Frankfurt, Paul-Ehrlich-Str. 40, 60596, Frankfurt am Main, Germany.
  • Lehr CM; Department of Genetics and Epigenetics, Saarland University, Campus A2 4, 66123, Saarbrücken, Germany.
Adv Sci (Weinh) ; 10(8): e2207301, 2023 03.
Article in English | MEDLINE | ID: covidwho-2228579
ABSTRACT
In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well as toxicological responses in humans. Models based on human cells and tissues are potential alternatives to animal experimentation allowing for the isolation of essential processes of human biology and making them accessible in vitro. Here, the generation of a novel monoclonal cell line "Arlo," derived from the polyclonal human alveolar epithelium lentivirus immortalized cell line hAELVi via single-cell printing, and its characterization as a model for the human alveolar epithelium as well as a building block for future complex in vitro models is described. "Arlo" is systematically compared in vitro to primary human alveolar epithelial cells (hAEpCs) as well as to the polyclonal hAELVi cell line. "Arlo" cells show enhanced barrier properties with high transepithelial electrical resistance (TEER) of ≈3000 Ω cm2 and a potential difference (PD) of ≈30 mV under air-liquid interface (ALI) conditions, that can be modulated. The cells grow in a polarized monolayer and express genes relevant to barrier integrity as well as homeostasis as is observed in hAEpCs. Successful productive infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a proof-of-principle study offers an additional, attractive application of "Arlo" beyond biopharmaceutical experimentation.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alveolar Epithelial Cells / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Adv Sci (Weinh) Year: 2023 Document Type: Article Affiliation country: Advs.202207301

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alveolar Epithelial Cells / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Adv Sci (Weinh) Year: 2023 Document Type: Article Affiliation country: Advs.202207301