Abstract
Mesenchymal stem cells (MSCs) are essential stromal regulators that coordinate tissue repair, angiogenesis, and immune balance. Within tumours, MSCs remodel the microenvironment and influence disease progression, yet their systemic contribution remains unclear due to the limited recovery of functional MSCs in conventional bone marrow transplantation models. Here, we developed an improved bone marrow collection (iBMC) method using enzymatic digestion, which markedly increases MSC yield while preserving their native phenotype. GFP bone marrow chimeric mice generated by iBMC and conventional transplantation displayed comparable hematopoietic reconstitution but differed in MSC abundance, enabling direct analysis of MSC-specific effects under physiological conditions. In mouse models of oral squamous cell carcinoma (OSCC), MSCs profoundly affected tumour development. MSC-deficient tumours exhibited necrosis and infiltration of immature myeloid-derived suppressor cells (MDSCs), whereas MSC-rich tumours showed enhanced vascularisation, adaptive immune infiltration, and stromal remodelling. Notably, lung metastasis occurred only in MSC-rich mice, accompanied by bone marrow–derived endothelial activation and TNF-α–driven inflammation. Pharmacological inhibition of LepR signalling using SHU9119 unexpectedly increased metastasis, underscoring the dual, context-dependent functions of MSCs. These findings establish iBMC as a reproducible and physiologically relevant model to study MSC-mediated regulation of tumour immunity, angiogenesis, and metastasis.
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We thank the teachers, professors, and colleagues from Okayama University who provided valuable advice and engaged in scientific discussions throughout the process.
Funding
This research is funded by JSPS KAKENHI (grant numbers JP23K09080, JP23K09332, JP23K09397, JP24K02644, JP24K13088, JP24K13130, JP22KK0275, and JP25KF0061).
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The authors declare no competing interests.
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All procedures performed in studies involving animals were in accordance with the ethical standards of the Okayama University Care and Use of Laboratory Animals guidelines and were approved by the Ethics of Animal Experiments Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (OKU2023534, OKU2024132). We stated that the protocol adheres to the ARRIVE guidelines for reporting animal experiments.
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Eain, H.S., Kawai, H., Sanou, S. et al. Metastatic promoting role of mesenchymal stem cells in oral squamous cell carcinoma revealed by an improved bone marrow chimeric model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-50837-z
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DOI: https://doi.org/10.1038/s41598-026-50837-z