Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical Stretch-Induced Lung Injury

Hochreiter, Beatrix and Lindner, Claudia and Postl, Matthias and Hunyadi-Gulyás Éva, Csilla and Darula, Zsuzsanna and Domenig, Oliver and Sharma, Smriti and Lang, Irene M. and Kiss, Attila and Spittler, Andreas and Hoetzenecker, Konrad and Reindl-Schwaighofer, Roman and Krenn, Katharina and Ullrich, Roman and Wieser, Matthias and Grillari-Voglauer, Regina and Tretter, Verena (2025) Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical Stretch-Induced Lung Injury. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (2). No. 683. ISSN 1661-6596

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Abstract

Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial cells from healthy donor lung tissue with the catalytic domain of telomerase and the SV40 large T/small t-antigen. These cells exhibited satisfactory growth characteristics and largely maintained their native characteristics, including morphology, cell surface marker expression, angiogenic potential and the protein composition of secreted extracellular vesicles. In order to test their suitability as a disease model, we simulated mechanical stress induced by cyclic stretch as encountered in ventilator-induced lung injury using the FlexCell® system and compared their performance to primary lung endothelial cells. In this setting, HLMVEC/SVTERT289 cells exhibited significantly higher neprilysin activity on the cell surface and extracellular vesicles secreted from the cell line exhibited higher Tissue Factor and ACE2 expression but lower ACE expression and ACE activity than vesicles released from the primary cells. This study provides an unprecedented and detailed characterization of the HLMVEC/SVTERT289 cell line, which should help to appraise its suitability in different molecular studies.

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