# Human bone marrow derived mesenchymal stem cells do not promote oral cancer cell growth in vitro and metastasis in vivo

## TL;DR

This study shows that bone marrow-derived stem cells do not promote oral cancer growth or spread, suggesting they could be safely used in regenerative treatments after cancer surgery.

## Contribution

The novel finding is that human bone marrow-derived mesenchymal stem cells do not enhance oral cancer progression in vitro or metastasis in vivo.

## Key findings

- BMMSC-conditioned medium did not significantly alter oral cancer cell proliferation or invasion in 3D assays.
- BMMSCs localized to the lungs in vivo but did not promote tumor growth or metastasis in xenografted mice.
- BMMSCs reduced oral cancer cell migration in 2D scratch wound assays.

## 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.

The online version contains supplementary material available at 10.1038/s41598-026-38370-5.