Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth

被引:67
作者
Chen, Yuxin [1 ]
Huang, Junfei [1 ]
Chen, Ruosi [1 ]
Yang, Lunan [1 ]
Wang, Jin [1 ]
Liu, Bingcheng [1 ]
Du, Lijuan [1 ]
Yi, Yanhua [1 ]
Jia, James [1 ]
Xu, Yanwei [2 ]
Chen, Qian [1 ]
Ngondi, Djakaya Guydidier [1 ]
Miao, Yong [1 ]
Hu, Zhiqi [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Plast & Aesthet Surg, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Cent Lab, Guangzhou 510515, Guangdong, Peoples R China
来源
THERANOSTICS | 2020年 / 10卷 / 03期
关键词
extracellular vesicles; oxidized sodium alginates; dermal papilla; hair regrowth; sustained release; STEM-CELLS; APPLYING MINOXIDIL; FOLLICLE; EXOSOMES; HYDROGELS; BIOLOGY; SYSTEM; REPAIR;
D O I
10.7150/thno.39566
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hair regeneration has long captured researchers' attention because alopecia is a common condition and current therapeutic approaches have significant limitations. Dermal papilla (DP) cells serve as a signaling center in hair follicles and regulate hair formation and cycling by paracrine secretion. Secreted EVs are important signaling mediators for intercellular communication, and DP-derived extracellular vesicles (DP-EVs) may play an important role in hair regeneration. However, the instability of EVs in vivo and their low long-term retention after transplantation hinder their use in clinical applications. Methods: Human DP-EVs were encapsulated in partially oxidized sodium alginate (OSA) hydrogels, yielding OSA-encapsulated EVs (OSA-EVs), which act as a sustained-release system to increase the potential therapeutic effect of DP-EVs. The ability of the OSA-EVs to protect protein was assessed. The hair regeneration capacity of OSA-EVs, as well as the underlying mechanism, was explored in hair organ culture and a mouse model of depilation. Results: The OSA-EVs were approximately 100 pm in diameter, and as the hydrogel degraded, DP-EVs were gradually released. In addition, the hydrogel markedly increased the stability of vesicular proteins and increased the retention of EVs in vitro and in vivo. The OSA-EVs significantly facilitated proliferation of hair matrix cells, prolonged anagen phase in cultured human hairs, and accelerated the regrowth of back hair in mice after depilation. These effects may be due to upregulation of hair growth-promoting signaling molecules such as Wnt3a and beta-catenin, and downregulation of inhibitory molecule BMP2. Conclusion: This study demonstrated that OSA hydrogels promote the therapeutic effects of DP-EVs, and indicate that our novel OSA-EVs could be used to treat alopecia.
引用
收藏
页码:1454 / 1478
页数:25
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