hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model.

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2024-01-20 DOI:10.1038/s41536-024-00349-z
Huiming Xu, Wei Jiang, Xuejia Li, Jiaohua Jiang, Shabbir Khan Afridi, Longhui Deng, Rui Li, Ermei Luo, Zhaoqing Zhang, Yu-Wen Alvin Huang, Yaxiong Cui, Kwok-Fai So, Haijia Chen, Wei Qiu, Changyong Tang
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Abstract

Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.

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通过抑制 ITGB3/ NF-κB 信号传导,源自 hUC 间充质干细胞的 MFGE8 可改善 NMO 小鼠模型的运动功能障碍。
神经脊髓炎(NMO)是一种严重的中枢神经系统自身免疫性炎症,会影响运动功能并导致复发性残疾。人脐带间充质干细胞(hUC-MSCs)具有缓解炎症和修复受损组织的强大调节作用,已被广泛用于治疗各种炎症性疾病。然而,目前它们在NMO中的应用还很有限,而且hUC-间充质干细胞对NMO运动功能产生有益影响的机制仍不清楚。在本研究中,我们研究了 hUC-间充质干细胞对 NMO 系统模型运动功能恢复的影响。我们的研究结果表明,hUC-间充质干细胞分泌的一种关键功能因子--乳脂球表皮生长8(MFGE8)在改善运动功能障碍方面发挥着关键作用。我们还阐明,MFGE8/表皮生长因子αvβ3/NF-κB 信号通路是结构和功能恢复的部分原因,此外,暴露于 hUC-MSCs 还可诱导运动功能增强。综上所述,这些发现有力地支持了 MFGE8 参与介导 hUC-间充质干细胞诱导的 NMO 小鼠模型运动功能恢复的改善。此外,这也为 hUC-间充质干细胞的治疗潜力及其对 NMO 的有益作用机制提供了新的见解。
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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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