Lee Seulbee, Hyun Donghun, Namkung Yong, Park Boram, Lee Byounggwan, Myung Junhyung, Hong Sunghoi
Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea.
BK21 FOUR R&E Center for Precision Public Health, Korea University, Seoul 02841, Republic of Korea.
Stem Cells. 2025 Jul 21;43(8). doi: 10.1093/stmcls/sxaf034.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and excessive immune activation. Conventional treatments using corticosteroids and immunosuppressants provide only temporary relief and often induce adverse side effects, highlighting the need for novel, effective therapy. In this study, we investigated the therapeutic potential of neural stem cell-derived extracellular vesicles (NSC-EVs) derived from NSC-derived conditioned medium (NSC-CM) in modulating inflammatory responses in AD. In vitro experiments using human keratinocytes (HaCaT) and murine macrophages (RAW264.7) showed that both NSC-CM and NSC-EVs can significantly decrease the expression of proinflammatory cytokines and chemokines, inhibit the phosphorylation of NF-κB, and reduce inducible nitric oxide synthase. In addition, topical application of NSC-CM and NSC-EVs alleviated atopic symptoms, reduced mast cell infiltration, and improved skin barrier integrity in a 2,4-dinitrochlorobenzene-induced AD mouse model. Proteomic analysis identified key proteins related to immune regulation and extracellular matrix remodeling in NSC-EVs, indicating their active role in mitigating inflammation and tissue repair. Altogether, our results demonstrated the potent anti-inflammatory effects of NSC-EVs, highlighting their potential to be a novel and effective therapeutic option for AD and other inflammation-related diseases.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其特征为表皮屏障功能受损和免疫过度激活。使用皮质类固醇和免疫抑制剂的传统治疗仅能提供暂时缓解，且常引发不良副作用，这凸显了对新型有效疗法的需求。在本研究中，我们调查了源自神经干细胞条件培养基（NSC-CM）的神经干细胞衍生细胞外囊泡（NSC-EVs）在调节AD炎症反应中的治疗潜力。使用人角质形成细胞（HaCaT）和小鼠巨噬细胞（RAW264.7）进行的体外实验表明，NSC-CM和NSC-EVs均可显著降低促炎细胞因子和趋化因子的表达，抑制NF-κB的磷酸化，并减少诱导型一氧化氮合酶。此外，在2,4-二硝基氯苯诱导的AD小鼠模型中，局部应用NSC-CM和NSC-EVs可减轻特应症状，减少肥大细胞浸润，并改善皮肤屏障完整性。蛋白质组学分析确定了NSC-EVs中与免疫调节和细胞外基质重塑相关的关键蛋白，表明它们在减轻炎症和组织修复中发挥积极作用。总之，我们的结果证明了NSC-EVs具有强大的抗炎作用，凸显了它们作为AD和其他炎症相关疾病新型有效治疗选择的潜力。
