Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth
Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth
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从可注射微凝胶中持续释放真皮乳头来源的细胞外囊泡可促进毛发生长
DOI：
10.7150/thno.39566
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Hu, Zhiqi
中科院分区：
文献类型：
--
作者：
Chen, Yuxin;Huang, Junfei;Hu, Zhiqi
毛发再生长期以来一直吸引着研究人员的注意，因为脱发是一种常见的疾病，目前的治疗方法有很大的局限性。毛乳头（DP）细胞作为毛囊中的信号中心，通过旁分泌调节毛发的形成和周期。分泌的EVs是细胞间通讯的重要信号介质，DP衍生的细胞外囊泡（DP-EVs）可能在毛发再生中发挥重要作用。然而，EV在体内的不稳定性和它们在移植后的低长期保留阻碍了它们在临床应用中的使用。研究方法：将人DP-EV包封在部分氧化的海藻酸钠（OSA）水凝胶中，产生OSA包封的EV（OSA-EV），其作为持续释放系统以增加DP-EV的潜在治疗效果。评估了OSA-EV保护蛋白质的能力。在毛发器官培养和小鼠脱毛模型中探索了OSA-EV的毛发再生能力以及潜在的机制。结果：所制备的OSA-EV直径约100 μm，随着水凝胶的降解，DP-EV逐渐释放。此外，水凝胶显着增加了囊泡蛋白的稳定性，并增加了EV在体外和体内的保留。OSA-EV显著促进毛基质细胞的增殖，延长培养的人毛发的生长期，并加速脱毛后小鼠背部毛发的再生。这些作用可能是由于毛发生长促进信号分子如Wnt 3a和β-连环蛋白的上调以及抑制分子BMP 2的下调。总结：该研究表明，OSA水凝胶促进了DP-EV的治疗效果，并表明我们的新型OSA-EV可用于治疗脱发。
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 μm 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 β-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.