Modelling Human Hair Follicles-Lessons from Animal Models and Beyond

Simple Summary Hair follicles are mini-organs in the skin that have regenerative cycles of growth, regression, and rest. The disruption of each phase in the hair cycle may cause hair-related issues such as hair loss. These defective events that occur in the hair cycle are well-studied in mice, but they are pending validation in humans due to limitations of current in vitro human hair models, whose improvement will add significant value to human hair research and hair loss treatment. However, it has been challenging to recreate the structural organization of highly diverse cell types that make up the hair follicle and its surrounding tissue in vitro. This review discusses the current knowledge of hair follicle formation and efforts to bioengineer hair follicles or hair-bearing skin in vitro.Abstract The hair follicle is a specialized appendage of the skin that is critical for multiple functions, including thermoregulation, immune surveillance, and sebum production. Mammals are born with a fixed number of hair follicles that develop embryonically. Postnatally, these hair follicles undergo regenerative cycles of regression and growth that recapitulate many of the embryonic signaling pathways. Furthermore, hair cycles have a direct impact on skin regeneration in homeostasis, cutaneous wound healing, and disease conditions such as alopecia. Here, we review the current knowledge of hair follicle formation during embryonic development and the post-natal hair cycle, with an emphasis on the molecular signaling pathways underlying these processes. We then discuss efforts to capitalize on the field's understanding of in vivo mechanisms to bioengineer hair follicles or hair-bearing skin in vitro and how such models may be further improved to develop strategies for hair regeneration.