Treatment with cyclohexyl salicylate, an olfactory receptor 2A4/7 agonist, promotes human hair follicle growth and bulge stem cell progeny expansion
381
Presented by: Janin Edelkamp
Introduction: Hair loss and thinning resulting from aging or hair follicle disorders, leads to severe psychological stress. Cosmetically and topically applicable strategies increasing hair density are highly demanded as alternative or adjuvant to drugs. Since the olfactory receptor (OR) 2AT4 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.
Methods: Using in situ hybridization and immunofluorescence staining, we aimed to characterize OR2A4/7 mRNA and protein expression in the hair follicle using fresh scalp skin immediately frozen after extraction. Furthermore, we organ cultured microdissected hair follicles in the presence of the cosmetic OR2A4/7 agonist, cyclohexyl salicylate (CHS) to study effects on hair cycle as well as hair follicle stem cells and progeny, applying immunofluorescence.
Results: 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, CHS treatment 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.
Discussion & Conclusion: Thus, stimulating OR2A4/7 via CHS promotes hair growth and expands the progeny of K15+ stem cells. Therefore, our data invite the use of CHS as a novel cosmetic to inhibit hair loss and thinning.
Methods: Using in situ hybridization and immunofluorescence staining, we aimed to characterize OR2A4/7 mRNA and protein expression in the hair follicle using fresh scalp skin immediately frozen after extraction. Furthermore, we organ cultured microdissected hair follicles in the presence of the cosmetic OR2A4/7 agonist, cyclohexyl salicylate (CHS) to study effects on hair cycle as well as hair follicle stem cells and progeny, applying immunofluorescence.
Results: 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, CHS treatment 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.
Discussion & Conclusion: Thus, stimulating OR2A4/7 via CHS promotes hair growth and expands the progeny of K15+ stem cells. Therefore, our data invite the use of CHS as a novel cosmetic to inhibit hair loss and thinning.