Advances in a rapidly emerging field of hair follicle stem cell research.

Human skin maintains the ability to regenerate during adulthood, as it constantly renews itself throughout adult life, and the hair follicle (HF) undergoes a perpetual cycle of growth and degeneration. The study of stem cells (SCs) in the epidermis and skin tissue engineering is a rapidly emerging field, where advances have been made in both basic and clinical research. Advances in basic science include the ability to assay SCs of the epidermis in vivo, identification of an independent interfollicular epidermal SC, and improved ability to analyze individual SCs divisions, as well as the recent hair organ regeneration via the bioengineered hair follicular unit transplantation (FUT) in mice. Advances in the clinic include recognition of the importance of SCs for wound repair and for gene therapy in inherited skin diseases, for example epidermolysis bullosa. The study of the HF stem cells (HFSCs) started by identification of epidermal SC in the HF bulge as quiescent "label retaining cells". The research of these cells emerged rapidly after the identification of bulge cell molecular markers, such as keratin 15 (K15) and CD34 in mice and CD200 in humans, which allowed the isolation and characterization of bulge cells from follicles. This paper provides an overview of the current knowledge on epidermal SCs in the HF describing their essential characteristics and the control of follicle SCs fate, their role in alopecia, as well as their use in tissue engineering.