1420 Ashwagandha-derived exosome-like nanoparticles promote human hair growth ex vivo

Novel strategies to inhibit hair loss are in high demand. Therapies using human-derived exosomes are currently being explored to promote hair growth with promising results, however the production of human-derived exosomes for large-scale use is proving challenging. Recently, the discovery that plant-derived exosome-like-nanoparticles may offer a valid substitute has opened new research venues. Here, we investigated whether this emerging therapy may be beneficial to modulate hair growth by selecting Ashwagandha, an herb traditionally used for improving overall health and relieving stress, as the source of plant-derived exosomes. Previously described Ashwagandha seed derived exosome-like nanoparticles (Ash-ELN) were applied to female and male microdissected human HFs ex vivo. Their impact on hair growth was assessed by analyzing hair cycle staging and hair shaft production by (immuno-)histomorphometry. Finally, RNAseq analysis was performed to identify signaling pathways involved in Ash-ELN-dependent hair cycle regulation. A significant increase in the number of anagen HFs was detected at the end of the culture. In line with this, hair shaft production was increased by Ash-ELN. Interestingly, an up-regulation of anagen promoting mRNAs, e.g. WNT10B, RSPO1 and VEGFD and down-regulation of the catagen inducers BMP4, DKK1 and TGFB1 was observed in at least 2 out of 3 donors analyzed. Taken together, our data reveal that Ash-ELN promotes hair growth ex vivoby modulating pathways involved in anagen/catagen transition, i.e. WNT, BMP, TGF and VEGF. Thus, our data invite the further exploration of plant-derived exosomes as alternative to human-originated nanoparticles for cosmeceutical and nutraceutical applications to reduce hair shedding.