Decellularized tongue tissue as an in vitro model for studying tongue cancer and tongue regeneration.

The decellularization of tissues or organs provides an efficient strategy for preparing functional scaffolds for tissue engineering. The microstructures of native extracellular matrices and biochemical compositions retained in the decellularized matrices provide tissue-specific microenvironments for anchoring cells. Here, we report the tongue extracellular matrix (TEM), which showed favorable cytocompatibility for normal tongue-derived cells and tongue squamous cell carcinoma (TSCC) cells under static or stirring culture conditions. Our results show that TEM retained tongue-specific integrated microstructures and abundant matrix components, which offer mechanical support and spatial signals for regulating cell behavior and function. Reconstructed TSCC by TEM presented characteristics resembling clinical TSCC histopathology, suggesting the possibility for TSCC research. In addition, TEM might be capable of guiding tongue-derived cells to the niche, benefiting cell survival, proliferation and differentiation. STATEMENT OF SIGNIFICANCE: In this study, we prepared decellularized tongue extracellular matrix (TEM) and evaluated the possibility for tongue squamous cell carcinoma (TSCC) research and tongue regeneration. TEM has six irreplaceable advantages: (1) tongue-specific intricate structures of TEM, which offer mechanical support for the cells; (2) abundant matrix components and spatial signals benefiting for cell attachment, survival, differentiation, and long-term viability of the highly functional phenotypes of tongue cells or TSCC cells; (3) reconstructed TSCC by TEM exhibited tumor heterogeneity, extremely resembling clinical TSCC histopathology; (4) ideal model to evaluate TSCC movement mode; (5) guiding tongue-derived cells to the site-appropriate niche; and (6) the possibility for static or stirred cell culture. These properties might be considered in TSCC research or tongue regeneration.