Understanding of the use of dermal papilla cells as a cell therapy for hair regeneration

Hair follicles develop as a result of reciprocal interactions [1] between clustered mesenchyme known as the condensate, and an epidermal thickening known as a placode. The condensate observed during development becomes the dermal papilla in the adult hair follicle, and just as the condensate drives hair follicle development, the dermal papilla is a key component of the adult follicle that promotes hair growth [2]. The hair follicle is also an important model system as it is a naturally regenerating organ structure. Every individual hair goes through a cycling process of growth, degeneration and regeneration in order to limit the length of the hair shaft. This cycling is under control of the dermal papilla and in each hair cycle in follicles suffering from androgenic alopecia, the number of mesenchymal cells in the dermal papilla is reduced resulting in a progressive miniaturisation of the hair shaft and the appearance of hair loss. Current hair transplantation can only take hairs that are not affected by androgenic alopecia and transplant them into affected areas. Although the cosmetic effect is helpful, the patient still has the same number after the procedure. Currently, there are no commercial systems which work to multiply the number of follicles on the scalp. As such, a lot of research focus has been on the adult dermal papilla which retains embryonic 'hair inducing' characteristics. When removed from the hair follicle and placed against non-follicular epithelium, the dermal papilla acts like a dermal condensate, and can induce de novo hair follicle growth in recipient epithelium [3]. However, as a strategy for hair loss, taking a single dermal papilla from a hair follicle and transplanting it so it induces a single hair, does not result in any improvement over current hair transplantation techniques. This does not result in an increase in overall hair follicle numbers. Dermal papilla can also be isolated from follicles and grown in culture resulting in an increase in their cell number, however, this results in a loss of their inductive capacity corresponding with a perturbed transcriptional signature [4]. We previously demonstrated that the transcriptional signature and inductive capacity of human dermal papilla cells could be partially restored, if the cells were grown in hanging drops promoting the formation of dermal spheroids [4]. Thus, as a cell therapy strategy, dermal papilla cells grown in 3D spheroids can induce de novo follicle regeneration. Using implanted cultured spheroids to combat hair loss would result in an increased number of hair follicles.