Treatment With Cyclohexyl Salicylate, an <scp>OR2A4</scp> /7 Agonist, Promotes Hair Growth and the Expansion of Epithelial Progenitor Cells in Human Hair Follicles Ex Vivo

Natural or synthetic non-drug agents activating olfactory receptors (OR) have great potential as adjuvant strategy for hair growth promotion. For instance, OR2AT4 activation prolongs anagen ex vivo and reduces telogen effluvium in vivo. We here targeted a further OR, OR2A4/7, and investigated whether its stimulation unfolds similar properties in human hair follicles (HFs). In fresh frozen scalp skin, OR2A4/7 mRNA was detected by in situ hybridization throughout the HF epithelium, while OR2A4/7 protein expression was restricted to the HF infundibulum. However, organ culture induced OR2A4/7 protein expression in the bulbar outer root sheath (ORS), hair matrix (HM), and dermal papilla (DP). A similar OR2A4/7 expression pattern was detected in affected HFs from male and female pattern hair loss patients. HF treatment ex vivo with cyclohexyl salicylate (CHS), a cosmetically applicable OR2A4/7 agonist, delayed catagen development and increased follicular CD34 and CD71 mRNA expression. In line, the percentages of the CD34+ epithelial HF stem cell immediate progeny and of the CD71+ transit amplifying cells, postulated to derive from CD34+ cells, was significantly increased by CHS. Thus, stimulation of OR2A4/7 with CHS promotes hair growth and expands epithelial HF stem cell progeny. Therefore, our data invites further exploration of CHS as a novel, non-drug strategy to treat hair loss disorders.