Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the impact of conditioned media (CM) on PM cell growth. All transduced derivatives exhibited elevated hTERT expression and activity, and increased mean telomere lengths. Cell morphology remained unchanged, and the proteomes were similar to the corresponding primary cells. Of note, the CM of primary and hTERT-transduced Meso-CAFs stimulated PM cell growth to the same extent, while CM derived from mesothelial cells had no stimulating effect, irrespective of hTERT expression. In conclusion, all new hTERT-transduced cell models closely resemble their primary counterparts and, hence, represent valuable tools to investigate cellular interactions within the TME of PM.
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http://dx.doi.org/10.3390/cells12152006 | DOI Listing |
Exp Cell Res
January 2025
Department of Maternal-Fetal Medicine Pregnancy Research Centre, Royal Women's Hospital, Parkville, VIC, 3052, Australia; University of Melbourne Department of Obstetrics and Gynaecology and Newborn Health, Royal Women's Hospital, Parkville, VIC, 3052, Australia. Electronic address:
Increasing evidence shows extracellular vesicles (EVs) are primarily responsible for the beneficial effects of cell-based therapies. EVs derived from mesenchymal stromal cells (MSCs) show promise as a source of EVs for cell-free therapies. The human placental fetal-maternal interface is a rich and abundant source of MSCs from which EVs can be isolated.
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August 2023
Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
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Unidad de Hepatología Experimental y Trasplante Hepático, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politecnico La Fe, Torre A. Lab 6.08, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain.
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December 2021
UOC di Oncologia Pediatrica, "Fondazione Policlinico Universitario A. Gemelli", IRCCS, Rome, Italy.
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View Article and Find Full Text PDFPLoS One
August 2017
Department of Chemical and Biomolecular Engineering, Particulate Fluids Processing Centre, The University of Melbourne, Parkville, Victoria, Australia.
Mesenchymal stem/stromal cells (MSCs) exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM) prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower) to produce the dECM drastically limits the utility and impact of this technology.
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