Hou Chongchao, Wang Sihua, Li Zihang, Huang Qing, Jiang Yang, Zhou Xin, Ou Rongying, Li Danyang, Xu Yunsheng
Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Regen Biomater. 2025 May 30;12:rbaf051. doi: 10.1093/rb/rbaf051. eCollection 2025.
Androgenetic alopecia (AGA) is a globally prevalent condition, with limited treatment options and significant adverse effects associated with existing therapies. The primary pathogenic mechanisms of AGA involve androgen-mediated regulatory pathways, molecular alterations affecting hair regeneration, and inflammation in the perifollicular microenvironment. In this study, we first investigated the topical application of testosterone with varied doses for AGA mouse model induction, in which the High-dose group exhibited the most robust model development and provided a more comprehensive set of criteria for successful AGA model establishment. Then, curcumin-primed milk-derived extracellular vesicles (Cur-mEVs) were fabricated for the therapy of AGA with the in-house developed mouse model described above. It was demonstrated that Cur-mEVs remodeled the hair follicle microenvironment, evidenced by the activation of the Wnt/β-catenin signaling pathway, downregulation of transforming growth factor beta 1 expression and alleviation of perifollicular inflammation. These effects collectively regulated the hair follicle cycle and promoted hair regeneration. Overall, our results highlighted a promising therapeutic approach for AGA with potential translational possibilities.
雄激素性脱发（AGA）是一种全球普遍存在的疾病，治疗选择有限，且现有疗法存在显著不良反应。AGA的主要致病机制涉及雄激素介导的调节途径、影响毛发再生的分子改变以及毛囊周围微环境中的炎症。在本研究中，我们首先研究了不同剂量睾酮的局部应用对AGA小鼠模型的诱导作用，其中高剂量组模型发育最为显著，为成功建立AGA模型提供了更全面的标准。然后，利用上述自行建立的小鼠模型，制备了姜黄素预处理的乳源细胞外囊泡（Cur-mEVs）用于AGA治疗。结果表明，Cur-mEVs重塑了毛囊微环境，表现为Wnt/β-连环蛋白信号通路的激活、转化生长因子β1表达的下调以及毛囊周围炎症的减轻。这些作用共同调节毛囊周期并促进毛发再生。总体而言，我们的结果突出了一种有前景的AGA治疗方法，具有潜在的转化应用可能性。
