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Objective: Head and neck region is involved in a high percentage of malignant lesions, and oral squamous cell carcinoma (OSCC) is undoubtedly the most frequently found, accounting for over 90% of malignant tumors. Hormone receptor overexpression, like Estrogen Receptor (ER), Progesterone Receptor (PR) and Endothelial Growth Factor Receptor (EGFR), and signaling have been related to the pathogenesis of OSCC. For metastasis of OSCC, Cancer Stem Cells (CSCs) undergo epithelial to mesenchymal transition (EMT) under the influence of growth factors, cytokines, and regulation of cadherins from the tumor's microenvironment. In this context, the stem cells may become a potential therapeutic target for OSCC through modulation of cytokines and RAS pathway, which is involved in intracell signal transduction. The objective of this study was to suggest an experimental steroidogenic model for OSCC in translational research., Patients and Methods: Dental-derived Stem Cells (D-dSCs) have been obtained from apical papilla tissue that surrounds the developing tooth of healthy donors and cultured in vitro. The cells have been exposed to different concentrations of Estradiol (E2 - 10 nM and 40 nM) in order to verify their response. The number of cells and cell viability has been evaluated up to 96 hours of treatment., Results: The results showed that cell growth was increased under estradiol treatments compared with cells maintained without estradiol. Moreover, no significant difference in cell death levels was detected among treatments., Conclusions: This work underlines as D-dSCs could represent a useful steroidogenic model for the development of the target and gene therapies in OSCC.