Liu Yukun, Liu Yonghong, Zhao Jing, Deng Tianyi, Ben Yinyin, Lu Ruitao, Zhou Xusha, Yan Runbin, Chen Xiaoqing, Zhang Jian V, Zhou Grace
Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Shenzhen International Institute for Biomedical Research, Shenzhen, China.
Front Bioeng Biotechnol. 2025 May 30;13:1614090. doi: 10.3389/fbioe.2025.1614090. eCollection 2025.
Androgenetic alopecia (AGA) is a common disorder that negatively impacts quality of life but remains challenging to treat effectively. The hair loss observed in AGA is the consequence of a gradual reduction in the duration of the anagen phase concomitant of the miniaturization of the hair follicles and subsequent atrophy. This process of miniaturization is associated with abnormalities in the Dihydrotestosterone (DHT) induced dermal papilla cells (DPCs). DHT induces DPCs senescence and promotes apoptosis of vascular endothelial cells and keratinocytes via the DPCs paracrine pathway, which ultimately leads to follicular miniaturization. In this study, we developed a multifunctional exosome-based targeted delivery platform, designated as EX104, through the engineering of HEK-293 cells to express a combination of therapeutical molecules, including WNT10B, VEGFA, and FGF7. EX104 reversed the hair follicle miniaturization phenotype in DHT-induced DPCs. Furthermore, it demonstrated significant hair growth-promoting effects in the murine model of androgenetic alopecia by remodeling the follicular microenvironment and restoring miniaturized hair follicles. Topical EX104 application demonstrated comparable hair growth promotion to first-line minoxidil, while significantly outperforming it in stimulating capillary growth and follicular proliferation. EX104 represents a promising and innovative strategy for AGA management and follicular regenerative therapy.
雄激素性脱发（AGA）是一种常见疾病，会对生活质量产生负面影响，但有效治疗仍具有挑战性。AGA中观察到的脱发是生长期持续时间逐渐缩短、毛囊逐渐变小并随后萎缩的结果。这种毛囊变小的过程与二氢睾酮（DHT）诱导的真皮乳头细胞（DPCs）异常有关。DHT通过DPCs旁分泌途径诱导DPCs衰老，并促进血管内皮细胞和角质形成细胞的凋亡，最终导致毛囊变小。在本研究中，我们通过对HEK-293细胞进行工程改造，使其表达包括WNT10B、VEGFA和FGF7在内的多种治疗分子，开发了一种基于多功能外泌体的靶向递送平台，命名为EX104。EX104逆转了DHT诱导的DPCs中的毛囊变小表型。此外，它通过重塑毛囊微环境和恢复变小的毛囊，在雄激素性脱发小鼠模型中显示出显著的促进头发生长的作用。局部应用EX104显示出与一线药物米诺地尔相当的促进头发生长效果，同时在刺激毛细血管生长和毛囊增殖方面明显优于米诺地尔。EX104代表了一种用于AGA管理和毛囊再生治疗的有前景的创新策略。
