Abstract
Mesenchymal stem cells (MSCs), particularly those derived from bone marrow (BMMSCs), hold substantial promise for bone regeneration in the maxillofacial region, especially after surgical resections with bone involvement. However, their use in patients with resections undergoing oral cancer treatment poses potential risks due to the effects of MSCs in modulating cancer cell behavior. This study aimed to assess the effect of circulatory BMMSCs on proliferation, migration, invasion, tumor growth, and metastasis of oral squamous cell carcinoma (OSCC) cells. Human BMMSCs were isolated, characterized, and their conditioned medium (CM) was tested on OSCC cell lines (Ca1 and OSCC1). Further, BMMSCs were transduced with lentiviral particles to express firefly luciferase for live cell tracking in vivo to study their biodistribution and homing capability to xenograft tongue tumors. In vitro assays revealed that BMMSC-CM did not significantly alter OSCC proliferation or invasion in 3D organotypic assays, while significantly reducing their migration in 2D scratch wound assay. In vivo, bioluminescent imaging and histological analyses indicated that human BMMSCs predominantly localized to the lungs without homing to other organs or to the human xenograft tongue tumors. Moreover, circulatory BMMSCs did not influence tumor size, nor did they promote lung metastasis in xenografted mice under these conditions. These findings suggest that circulating BMMSCs did not exacerbate OSCC progression, supporting their potential use in regenerative applications for patients post-OSCC resection.
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Acknowledgements
The authors would like to acknowledge the Flow Cytometry Core Facility, Department of Clinical Science, University of Bergen for their assistance in acquisition.
Funding
Open access funding provided by University of Bergen. The authors declare that financial support was received from the Research Council of Norway through its Centers of Excellence funding scheme, (DEC and HND, Grant No. 22325 to Center of Excellency for Cancer Biomarkers CCBIO) and The Western Norway Regional Health Authority (DEC, Helse Vest Grant Nos 912260/2019 and F-13105/2024). The authors also acknowledge the Trond Mohn Foundation (KBEM, OsteoStem Grant No. TMS2021TMT08) for financial support.
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Conceptualization, DS, HP, KM, DEC and HND; data curation, DS, HP, IEH, DK, LL, SMA and HND.; formal analysis, DS, HP and HND; funding acquisition, HR, KM, DEC and HND; investigation, DS, HP, IEH, DK, LL, SMA, DEC and HND.; methodology, DS, HP, DEC and HND.; project administration, HR, KM, DEC and HND.; supervision, HP, DEC and HND.; validation, DS, HP and HND; visualization, DS, HP and DEC; writing—original draft, DS and HND; writing—review & editing, DS, HP, HR, SMA, KM, DEC and HND. All authors have read and agreed to the published version of the manuscript.
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Appropriate informed consent was obtained from all donors and the study was approved by the Regional Committee for Medical Research Ethics (REK), Norway (2013–1248/REK-sør-øst C and 2016-1266/REK-nord).
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Siyam, D., Parajuli, H., El herch, I. et al. Human bone marrow derived mesenchymal stem cells do not promote oral cancer cell growth in vitro and metastasis in vivo. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38370-5
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DOI: https://doi.org/10.1038/s41598-026-38370-5
