Stem cells that maintain and regenerate lingual keratinized epithelial cells.

Abstract

Lingual epithelial cells, which constitute the filiform papillae of the tongue are thought to be an origin of the Tongue Cancer. And lingual tissues have one of the most rapid tissue turnover rates in the mammalian body. However, the mechanism of tissue maintenance and regeneration is not well known for these tissues. Here, we show that Bmi1- postitive cells within Cytokeratin14 and Cytokeratin5-positive cells are present in the base but not at the very bottom of the inter-papillary pit as a stem cell. And we demonstrated that one stem cell per inter-papillary pit survives longterm by using a multicolor lineage tracing method. The cells were found to usually be in a slow-growing or resting state; however, on irradiation-induced injury, the cells rapidly entered the cell cycle and regenerated tongue epithelium. The elimination of Bmi1-positive stem cells significantly suppressed the regeneration after irradiation injury. Then we show the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors in vitro. The organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice. Taken together, these results suggest that Bmi1-positve cells are important for tissue maintenance and regeneration of the lingual epithelium.