732 Treatment with cyclohexyl salicylate, an olfactory receptor 2A4/7 agonist, promotes human hair follicle growth and bulge stem cell progeny expansion

Abstract

Topically applicable non-drugs that enhance the efficacy of available FDA-licensed drugs would be a welcome therapeutic addition in hair loss management. Since the olfactory receptor (OR) agonist, Sandalore, promotes human hair growth and reduces telogen effluvium, we have explored here whether other cosmetic OR ligands can unfold similar properties. We focused on OR2A4/7, since its stimulation promotes epidermal keratinocyte proliferation and differentiation. In situ hybridization showed that OR2A4/7 mRNA is widely expressed in the hair follicle (HF) epithelium, namely the outer root sheath (ORS) and hair matrix (HM). Yet, in freshly embedded human scalp skin, OR2A4/7 protein was mainly restricted to the infundibulum. However, OR2A4/7 protein became widely expressed in the ORS and HM during HF organ culture (OC), suggesting up-regulation of intrafollicular OR2A4/7 expression under tissue stress conditions. In scalp HF OC, the cosmetic OR2A4/7 agonist, cyclohexyl salicylate (CHS), delayed catagen development and tendentially increased HM proliferation. While CHS did not seem to impact on K15+ bulge stem cells, the % of CD34+ cells, i.e. their immediate progeny, was significantly increased in the suprabulbar ORS, as was the % of CD71+ transit amplifying cells (thought to derive from CD34+ cells) in the HM and suprabulbar ORS. Thus, stimulating OR2A4/7 via the non-drug CHS promotes hair growth and expands the progeny of K15+ stem cells, inviting the use of CHS as a novel cosmetic adjuvant treatment for hair loss disorders characterized by premature catagen development and a reduced capacity of K15+ stem cells to generate progeny, such as androgenetic alopecia.