Department of Veterinary Clinical Pathology, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon-do, 24341, Republic of Korea.
Bioanalysis Center, GenNBio Inc, 700, Daewangpangyo-ro, Bundang-gu, Seongnam-Si, Gyeonggi-do, 13488, Republic of Korea.
Arthritis Res Ther. 2024 Nov 18;26(1):201. doi: 10.1186/s13075-024-03435-1.
Systemic lupus erythematosus (SLE) is an incurable chronic autoimmune disease of unknown etiology. Therefore, the development of new treatments is urgently needed. This study aimed to investigate the therapeutic effects of extracellular vesicles (EV) derived from immortalized mesenchymal stem cells (iMSCs) primed with conditioned media obtained from disease-conditioned immune cells (CM-EV) and iMSC-derived EV (ASC-EV) in a murine model of SLE.
Female NZB/W F1 mice were divided into the control (C, n = 15), ASC-EV (E, n = 15), and CM-EV (CM, n = 15) groups. Mice in the C, E, and CM groups were intravenously administered saline, ASC-EV, and CM-EV, respectively, once weekly from 6 to 42 weeks of age.
Compared to the ASC-EV, the CM-EV showed a significant increase in TGF-β1 production and miR-155-5p and miR-142-3p expression. CM-EV treatment increased survival, decreased anti-dsDNA antibody levels, and ameliorated renal histopathology. Although ASC-EV treatment significantly reduced the incidence of severe proteinuria and improved renal histopathology, it did not significantly improve survival rate. ASC-EV or CM-EV treatment significantly decreased the proportion of pro-inflammatory macrophages (CD11c + CD206-; M1) and M1:M2 ratio. Additionally, CM-EV treatment significantly increased the expression of anti-inflammatory macrophages (CD11c-CD206 + ; M2). Moreover, CM-EV treatment significantly decreased the expression of lupus-specific miRNAs (miR-182-5p and miR-183-5p) in the spleen.
EV derived from iMSCs primed with conditioned media obtained from disease-conditioned immune cells exert immunomodulatory effects and ameliorate SLE in a murine model.
系统性红斑狼疮（SLE）是一种病因不明的无法治愈的慢性自身免疫性疾病。因此，迫切需要开发新的治疗方法。本研究旨在探讨经疾病状态免疫细胞条件培养基诱导的永生化间充质干细胞（iMSC）衍生的细胞外囊泡（EV）（CM-EV）和 iMSC 衍生的 EV（ASC-EV）在 SLE 小鼠模型中的治疗效果。
将雌性 NZB/W F1 小鼠分为对照组（C，n=15）、ASC-EV 组（E，n=15）和 CM-EV 组（CM，n=15）。C、E 和 CM 组小鼠分别于 6 至 42 周龄时每周静脉注射生理盐水、ASC-EV 和 CM-EV。
与 ASC-EV 相比，CM-EV 表现出 TGF-β1 产生和 miR-155-5p、miR-142-3p 表达的显著增加。CM-EV 治疗增加了存活率，降低了抗 dsDNA 抗体水平，并改善了肾脏组织病理学。虽然 ASC-EV 治疗显著降低了严重蛋白尿的发生率并改善了肾脏组织病理学，但对存活率无显著影响。ASC-EV 或 CM-EV 治疗显著降低了促炎巨噬细胞（CD11c+CD206-；M1）的比例和 M1:M2 比值。此外，CM-EV 治疗显著增加了抗炎巨噬细胞（CD11c-CD206+；M2）的表达。此外，CM-EV 治疗显著降低了脾脏中狼疮特异性 miRNAs（miR-182-5p 和 miR-183-5p）的表达。
经疾病状态免疫细胞条件培养基诱导的 iMSC 衍生的 EV 发挥免疫调节作用，并改善 SLE 小鼠模型的疾病。
