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Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical
Beatrix Hochreiter1, Claudia Lindner2, Matthias Postl2
1Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anesthesia, Genera Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria.
International Journal of Molecular Sciences
|January 25, 2025
Summary
A novel human cell line (HLMVEC/SVTERT289) was developed for preclinical research. This cell line mimics native lung endothelial cells and shows promise for studying lung injury models.
Area of Science:
- Cell Biology
- Preclinical Research Models
- Endothelial Cell Biology
Background:
- Preclinical models are crucial for drug development, bridging cell cultures/animal studies and human clinical trials.
- Existing models often have limitations in fully recapitulating human physiological conditions.
Purpose of the Study:
- To generate and characterize a novel human lung microvascular endothelial cell line (HLMVEC/SVTERT289).
- To evaluate the suitability of this cell line as a disease model, particularly for ventilator-induced lung injury.
- To compare the HLMVEC/SVTERT289 cell line's response to mechanical stress with primary lung endothelial cells.
Main Methods:
- Transfection of primary human lung microvascular endothelial cells with telomerase catalytic domain and SV40 large T/small t-antigen.
- Assessment of cell growth, morphology, surface marker expression, and angiogenic potential.
- Simulation of mechanical stress using cyclic stretch (FlexCell® system).
- Analysis of cell surface neprilysin activity and extracellular vesicle protein expression (Tissue Factor, ACE2, ACE).
Main Results:
- The HLMVEC/SVTERT289 cell line demonstrated robust growth and maintained key native characteristics.
- Under simulated mechanical stress, HLMVEC/SVTERT289 cells showed higher cell surface neprilysin activity compared to primary cells.
- Extracellular vesicles from HLMVEC/SVTERT289 cells exhibited increased Tissue Factor and ACE2 expression, but decreased ACE expression and activity.
Conclusions:
- The HLMVEC/SVTERT289 cell line is a well-characterized preclinical model with retained endothelial characteristics.
- This cell line offers a valuable tool for studying lung endothelial cell responses to mechanical stress and associated molecular changes.
- Its unique profile in extracellular vesicle composition suggests potential applications in modeling specific aspects of lung injury and disease.
