Effects of the PI3K/Akt signaling pathway on the hair inductivity of human dermal papilla cells in hair beads

• DOI: 10.1016/j.jbiosc.2022.03.010
• Publication Date: 2022-04-14T21:06:05Z
• Authors: Monami Yamane; Jieun Seo; Yinghui Zhou; Tomoki Asaba; Shan Tu; Ayaka Nanmo; Tatsuto Kageyama; Junji Fukuda
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Humans; Collagen; Phosphatidylinositol 3-Kinase; Hair Follicle; Proto-Oncogene Proteins c-akt; Cells, Cultured; Cell Proliferation; Hair; Signal Transduction; 3. Good health

Dermal papilla cells (DPCs), which play a central role in the regulation of hair follicle development and hair growth, are among the most promising cell sources for hair regenerative medicine. However, a critical issue in the use of DPCs is the immediate loss of hair inducing functions in typical two-dimensional (2D) culture. We have previously demonstrated that when DPCs are encapsulated in drops of collagen gel (named hair beads, HBs), the density of collagen and cells is concentrated >10-fold during 3 d of culture through the spontaneous constriction of the drops, leading to efficient hair follicle regeneration upon transplantation. However, the mechanisms responsible for the activation of the hair-inducing functions of DPCs have been poorly elucidated. Here, transcriptome comparisons of human DPCs in HB culture and in typical 2D culture revealed that the phosphoinositide 3-kinase and Akt (PI3K/Akt) signaling pathway was significantly upregulated in HB culture. Inhibition of the PI3K/Akt signaling pathway decreased the hair-inducing capability of DPCs in HBs, while the activation of the PI3K/Akt signaling pathway using an activator improved trichogenous gene expression of DPCs in 2D culture. These results suggest that the PI3K/Akt signaling pathway is crucial for the maintenance and restoration of hair inductivity of DPCs. HB culture and/or activators of the PI3K/Akt signaling pathway could be a promising strategy for preparing DPCs for hair regenerative medicine.