脂肪来源干细胞分泌的外泌体是治疗免疫介导性脱发的潜在治疗剂。
Exosomes Secreted from Adipose-Derived Stem Cells Are a Potential Treatment Agent for Immune-Mediated Alopecia.
机构信息
Department of Dermatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
School of Medicine, Tongji University, Shanghai 200092, China.
出版信息
J Immunol Res. 2022 Feb 3;2022:7471246. doi: 10.1155/2022/7471246. eCollection 2022.
BACKGROUND
Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth and for potentially treating immune-mediated alopecia and further exploring the underlying mechanism.
METHODS
Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established ; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real-time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq).
RESULTS
ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF- signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice.
CONCLUSION
ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/-catenin signaling pathway, and the TNF- signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.
背景
脱发已成为一种极其普遍的皮肤科疾病。病因上，感染（细菌和真菌感染）、炎症和免疫失调是免疫介导性脱发的主要原因。由于现有的治疗方法有限，治疗脱发仍然具有挑战性。脂肪源性干细胞（ADSC-Exos）来源的外泌体已被用于治疗神经退行性疾病和自身免疫性疾病以及伤口愈合治疗。然而，ADSC-Exos 在脱发治疗中的作用和机制尚不清楚。本研究旨在探讨 ADSC-Exos 对毛发生长的影响，并有可能治疗免疫介导性脱发，进一步探讨其潜在机制。
方法
通过细胞计数试剂盒-8（CCK-8）检测、划痕愈合检测和流式细胞术分别检测 ADSC-Exos 处理的真皮乳头细胞（DPC）的细胞增殖、迁移和凋亡。建立 C57BL/6 脱发小鼠模型；然后，单独或联合使用米诺地尔皮下注射 ADSC-Exos。通过 HE 染色、实时定量 PCR（qRT-PCR）、western blot 和 RNA 测序（RNA-seq）研究 ADSC-Exos 对毛发生长、病理变化及相关机制的影响。
结果
ADSC-Exos 显著促进 DPC 增殖和迁移，同时减少凋亡。此外，与对照组相比，ADSC-Exos 处理的小鼠毛发生长更好，毛囊和真皮更厚。RNA-seq 显示，ADSC-Exos 处理后 DPC 中的 miR-22 和 TNF-信号通路明显下调。此外，根据 qRT-PCR 和 western blot 结果，ADSC-Exos 处理小鼠皮肤中的 Wnt/-catenin 信号通路被激活。
结论
ADSC-Exos 治疗通过调节 miR-22、Wnt/-catenin 信号通路和 TNF-信号通路，对促进毛发生长产生积极影响，这表明 ADSC-Exos 可能是一种有前途的免疫介导性脱发无细胞治疗策略。
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