Mesenchymal stem cell transplantation attenuates growth of chemotherapy treated oral squamous cell carcinoma in an animal model.

BACKGROUND: Recent studies have demonstrated mesenchymal stem cell migration toward tumor locations. When applied locally, MSCs interact with the locally residing host cells. The mechanisms behind this are still unclear. We aimed to detect the possible action mechanisms of MSCs on the in vivo growth of primary human oral squamous cell carcinoma. METHODS: In mouse model of OSSC, chemotherapy with Cisplatin was done beginning from 9 day of tumor visualization. 3 weeks after tumor cell injection cultivated MSCs were administrated in tail vein or directly intra-tumorally. Animals underwent surveillance and afterward were sacrificed. Tumor growth was measured. MSCs biodistribution was assessed with bioluminescent analysis. Tumor tissues were tested morphologically and immunohistochemically for angiogenesis, hypoxia status, and cell apoptosis. RESULTS: In the group treated with Cisplatin in combination with mesenchymal stem cell injection, the average size of the tumor was 98.9 +/- 7.65 mm(3) . In the experimental group, tumor tissues were less outlined and the presence of necrotic areas and connective tissue basal layers was detected. Immunohistochemical surveys with CD31 and anti-carbonic anhydrase 9 demonstrated strongly developed micro-vessel structures and small isles of hypoxia in the tumor tissues. TUNEL assay revealed in the same group that tumor tissues were mostly comprised of apoptotic cells. Viable cell communities presented as small isles. CONCLUSION: The study demonstrates that intra-tumorally injected MSCs, combined with Cisplatin, leads to a minimal hypoxia status and increased apoptotic activity in tumor tissues, compared with the control group. This finding can be explained with better distribution of Cisplatin due to increased angiogenesis.