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

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. (c) 2022, The Society for Biotechnology, Japan. All rights reserved.

Automated summary

Transcriptome comparisons of dermal papilla cells (DPCs) in hair beads (HB) culture and typical 2D culture revealed the upregulation of the phosphoinositide 3-kinase and Akt (PI3K/Akt) signaling pathway in HB culture. Inhibition of this pathway decreased the hair-inducing capability of DPCs in HBs, while activation of the pathway improved trichogenous gene expression of DPCs in 2D culture.