Platelet-rich plasma-derived exosomes stimulate hair follicle growth through activation of the Wnt/β-Catenin signaling pathway
Changpei Lu, Yunbu Ding, Rongshuang Zhang, Yimei Du, Lingbo Bi, Min Zhao, Chaofan Wang, Qiaofang Wu, Haixia Jing, Weixin Fan
Abstract
Androgenetic alopecia (AGA) is a common type of hair loss that affects a large segment of the global population, significantly influencing individuals' appearance and mental health. Existing treatments like minoxidil and finasteride have limited effectiveness and can cause side effects, highlighting the need for alternative therapies. This study aims to explore the effectiveness of platelet-rich plasma-derived exosomes (PRP-Exos) in stimulating hair follicle growth and the proliferation of human dermal papilla cells (DPCs), as well as to investigate the mechanisms involved. PRP-Exos were isolated and characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. The impact of PRP-Exos on DPC proliferation was measured using CCK-8 assays, while their migration was assessed through Transwell migration and scratch wound healing assays. Flow cytometry was used to analyze cell cycle progression. Hair follicle organ culture was employed to examine the effects of PRP-Exos on hair follicle growth, and in vivo experiments were conducted in a mouse model to assess the influence of PRP-Exos on hair follicles. DPCs internalized PRP-Exos, which significantly boosted their proliferation and migration, as shown by CCK-8, Transwell migration, and scratch wound healing assays. Flow cytometry revealed that PRP-Exos facilitated cell cycle progression in DPCs. Furthermore, treatment with PRP-Exos resulted in increased levels of β-Catenin and Lef-1, along with decreased expression of SFRP1, indicating activation of the Wnt/β-Catenin pathway. Hair follicle organ culture indicated enhanced hair follicle growth and a prolonged anagen phase, delaying the transition to the telogen phase. In vivo studies demonstrated increased skin thickness, hair follicle diameter, and a favorable anagen-to-telogen ratio in mice, promoting hair growth during the telogen phase. PRP-Exos show promise as a therapeutic option for AGA by stimulating hair follicle growth through the activation of the Wnt/β-Catenin signaling pathway. These findings suggest that PRP-Exos could enhance hair follicle regeneration both in vitro and in vivo. • First Comprehensive Study on PRP-Exos in Hair Restoration : This research is the first to explore the therapeutic effects of platelet-rich plasma-derived exosomes (PRP-Exos) on hair follicle growth, addressing a significant gap in the current literature. • Activation of the Wnt/β-Catenin Signaling Pathway : The study reveals that PRP-Exos stimulate hair follicle growth by activating the Wnt/β-Catenin pathway, a key mechanism in hair regeneration. • Holistic Experimental Approach : The research employs a multi-faceted design, including in vitro studies on dermal papilla cells (DPCs), ex vivo hair follicle organ cultures, and in vivo animal models, providing a comprehensive understanding of PRP-Exos' effects. • Clinical Relevance and Potential Impact : The ability of PRP-Exos to stimulate hair follicle growth and prolong the anagen phase presents a promising therapeutic avenue for AGA patients, especially those seeking alternatives to traditional treatments like minoxidil and finasteride, which are often associated with side effects.