Stimulation of the KLF4 pathway by bee products modulates the progression of hair anagen to telogen molecular switch.
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Presented by: Nico Forraz
INTRODUCTION: Medicines containing natural bee products are gaining more and more attention. Numerous studies have now proven the positive benefits of bee products for medical treatments but also as cosmetic ingredients. Each bee product possesses specific components which determine their activities. Honey contains more than 180 ingredients making each honey singular with unique properties. Royal jelly contains carbohydrates and amongst others amino acids, proteins, lipids, vitamins making this bee product a key element. Skin biology has also linked the epidermal-hair axis as an active and effective route for ingredient interaction for regeneration. Here we developed an accurate hair follicle – dermis – epidermis model to effectively evaluate hair phase kinetics through to promotion of coloration in the epidermis and hair itself.
METHODS: Human scalp samples with hair follicles were obtained from local hospitals following elective surgery and ethical consent. Uniform ex vivo samples with approximately uniform numbers of follicles were created and placed into skin culture medium for maintenance. Four honeys from Ouessant, Corsica, Aland and Ikaria islands and a royal jelly (all with biological activities previously demonstrated) were selected and tested in combination. The bee products were mixed and placed into growth medium and prepared daily before use. Samples were cultured for 10 days, with application each day of the product or control (medium alone) to the scalp surface evenly. Viability of the sample was assessed at Day1, 3, 6 and 10 using the Alamar Blue resazurin conversion and spectrophotometry. At Day 10 samples were OCT processed for histology, assessing both basic structure with HES and immuno-histological staining of 8 specific markers: FGF9, IGF-1, FGF5, KLF4, FGF7, TGF beta, Versican and KGFR to evaluate epidermal and hair follicle kinetics.
RESULTS AND DISCUSSION: Overall no difference in viability of the samples was observed between conditions, with a lower viability by Day 10 as expected with human ex vivo samples. Structural changes compared to control were not seen in the dermis, but hydrative effects were visible in the epidermis and a promotion of melanin in the hair follicles. Immunofluorescence, however, was remarkable, showing a promotion of proliferation in the hair bulb stem cells with KLF4 expression increase, whilst the lower FGF5 and TGF expression is consistent with a movement away from telogen. Versican, FGF7, IGF1 were also slightly higher in the hair bulb area consistent with promotion of anagen phase and mediation of hair growth to the follicle from fibroblasts. In the epidermis, increased expression of KGFR, KLF4, FGF7 and TGF indicated a higher level of differentiation-maturation cycling and turnover of keratinocytes promoting a thicker more proliferative epidermis, without dysregulation.
CONCLUSIONS: Taken together, these results demonstrate that this combination of bee products has beneficial effects on both epidermal and hair follicle, making this association a good candidate for cosmetics products and opens the way to further investigation. At the same time, this study reveals that our ex vivo model and strategy represent an interesting approach for testing cosmetic actives dedicated to scalp and hair care.
METHODS: Human scalp samples with hair follicles were obtained from local hospitals following elective surgery and ethical consent. Uniform ex vivo samples with approximately uniform numbers of follicles were created and placed into skin culture medium for maintenance. Four honeys from Ouessant, Corsica, Aland and Ikaria islands and a royal jelly (all with biological activities previously demonstrated) were selected and tested in combination. The bee products were mixed and placed into growth medium and prepared daily before use. Samples were cultured for 10 days, with application each day of the product or control (medium alone) to the scalp surface evenly. Viability of the sample was assessed at Day1, 3, 6 and 10 using the Alamar Blue resazurin conversion and spectrophotometry. At Day 10 samples were OCT processed for histology, assessing both basic structure with HES and immuno-histological staining of 8 specific markers: FGF9, IGF-1, FGF5, KLF4, FGF7, TGF beta, Versican and KGFR to evaluate epidermal and hair follicle kinetics.
RESULTS AND DISCUSSION: Overall no difference in viability of the samples was observed between conditions, with a lower viability by Day 10 as expected with human ex vivo samples. Structural changes compared to control were not seen in the dermis, but hydrative effects were visible in the epidermis and a promotion of melanin in the hair follicles. Immunofluorescence, however, was remarkable, showing a promotion of proliferation in the hair bulb stem cells with KLF4 expression increase, whilst the lower FGF5 and TGF expression is consistent with a movement away from telogen. Versican, FGF7, IGF1 were also slightly higher in the hair bulb area consistent with promotion of anagen phase and mediation of hair growth to the follicle from fibroblasts. In the epidermis, increased expression of KGFR, KLF4, FGF7 and TGF indicated a higher level of differentiation-maturation cycling and turnover of keratinocytes promoting a thicker more proliferative epidermis, without dysregulation.
CONCLUSIONS: Taken together, these results demonstrate that this combination of bee products has beneficial effects on both epidermal and hair follicle, making this association a good candidate for cosmetics products and opens the way to further investigation. At the same time, this study reveals that our ex vivo model and strategy represent an interesting approach for testing cosmetic actives dedicated to scalp and hair care.