Kosé and Niigata University Develop 3D-Epithelial Model For Human Lips

Kosé Corporation and a Niigata University professor and his team have developed a three-dimensional epithelial model that reproduces the human lip, the area from the oral mucosa to the lips and surrounding skin, using cell culture.

Kosé and the resaerchers says this will make it possible to verify efficacy and safety evaluations of cosmetic ingredients and products on a structure more similar to the actual lip area, which has been limited until now to verification using standard skin and oral mucosa in vitro models.

The results of this research have been published online in the scientific journal Histochemistry and Cell Biology in June 2023.

The lip area has the transition area between the facial skin and the oral mucosa, and has a unique structure and properties that differ from both of them, such as the stratum corneum being thinner and more delicate than in skin. The development of lip area models that reproduce its unique structure and their use for functional analysis of the lip area and evaluation of formulations and ingredients, is a useful tool to promote better formulation development, according to Prof. Izumi of Niigata University Graduate School of Medical and Dental Sciences.

The research group used only cells derived from the epidermis and oral mucosal epithelium to develop a three-dimensional model with characteristics similar to those of the human lip area.

To reproduce the lips part, a technique was used in which cells derived from skin and oral mucosa coexist. First, cells derived from skin and oral mucosa were seeded on both sides of a divider, and the divider was then removed to allow spontaneous migration (movement to another position) of the cells from both sides to the area where the divider was. Subsequently, the lip area-equivalent part was prepared by culturing the cells in air (Fig. 2). Tissue staining of the constructed lip area model revealed that the cells have structures and features similar to actual skin, lip areas, and oral mucosa, respectively (Fig. 1).

Since it is known that the mechanism of cell differentiation (mode of differentiation), which is the process of cell maturation, differs between the skin, lips, and oral mucosa, the mode of differentiation was confirmed in the lip area model created. The lip area model was stained for keratin 2e (KRT2) and small proline-rich protein 3 (SPRR3), proteins representing differing modes of differentiation in cells derived from skin and oral mucosa, respectively. The results were that KRT2 was more abundant on the skin side, decreased in the lip area-equivalent part, and disappeared on the oral mucosa side (Fig. 3, red). On the other hand, SPRR3 was found to be more abundant on the oral mucosa side, and decreased toward the lip area-equivalent part and skin side (Fig. 3, green). This differentiation mode is similar to that of actual human lip area tissue, confirming that the lip area model developed has a similar differentiation mode to that of the human lip area.

From the above, it is concluded that the lip area model developed in this research has a similar structure and differentiation mode to that of actual human lip area tissue, and it is expected to be used for evaluation of the effects of cosmetic ingredients on the lip area and other purposes.

The lip area model developed in this research will be used for basic research on the lips, which has only been possible until now with alternative methods using skin and oral mucosa, and for future development of lip care products and ingredients.