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VCAM-1 间充质干细胞/基质细胞在实验性自身免疫性脑脊髓炎多发性硬化症小鼠模型中比 VCAM-1 对照物显示出更好的疗效。

VCAM-1 Mesenchymal Stem/Stromal Cells Reveal Preferable Efficacy Upon an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis Over the VCAM-1 Counterpart.

机构信息

Department of Neurology, The Second Hospital of Shandong University, 247 Beiyuan Road, Jinan, China.

Department of Neurology, Weihai Municipal Hospital, Weihai, China.

出版信息

Neurochem Res. 2024 Nov 30;50(1):40. doi: 10.1007/s11064-024-04267-w.

DOI:10.1007/s11064-024-04267-w
PMID:39613932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11607028/
Abstract

Despite the considerable progress in mesenchymal stem/stromal cells (MSCs)-based novel intervention of multiple sclerosis (MS), yet the disease-modifying effect of VCAM-1 MSCs and novel VCAM-1 counterpart is largely obscure. In this study, we took advantage of the EAE mouse model and VCAM-1 human umbilical cord-derived MSCs (hUC-MSCs) for the evaluation of the therapeutic effect of systematic MSCs infusion. On the one hand, we compared the protective effect of VCAM-1 and VCAM-1 hUC-MSCs against the clinical symptoms, demyelination, active glia cells and neuroinflammation in EAE mice by conducting multifaceted detections upon spinal cord and brain tissues. On the other hand, we conducted RNA-sequencing (RNA-SEQ) and multidimensional bioinformatics analyses for the evaluation of the transcriptomic features of spinal cord tissue in EAE mice after systematic hUC-MSCs infusion. Compared to those with VCAM-1 hUC-MSCs injection, VCAM-1 mice showed further remission in clinical manifestations, and in particular, the inflammatory infiltration and active glial cells. Mice in all groups revealed conservations in overall gene expression profiling and somatic mutation spectrum. The differentially expressed genes (DEGs) between EAE mice and those with hUC-MSCs infusion were mainly involved in neuroinflammation and inflammatory response. Our findings indicated the feasibility of VCAM-1 hUC-MSCs for multiple sclerosis treatment, which would supply new references for the development of novel VCAM-1 MSCs-based cytotherapy in future.

摘要

尽管间充质干细胞(MSCs)为基础的新型多发性硬化症(MS)干预方法取得了相当大的进展,但 VCAM-1 MSCs 和新型 VCAM-1 对应物的疾病修饰作用在很大程度上仍不清楚。在这项研究中,我们利用 EAE 小鼠模型和 VCAM-1 人脐带衍生的间充质干细胞(hUC-MSCs)评估系统间充质干细胞输注的治疗效果。一方面,我们通过对脊髓和脑组织进行多方面检测,比较了 VCAM-1 和 VCAM-1 hUC-MSCs 对 EAE 小鼠临床症状、脱髓鞘、活性神经胶质细胞和神经炎症的保护作用。另一方面,我们进行了 RNA 测序(RNA-SEQ)和多维生物信息学分析,以评估 EAE 小鼠系统输注 hUC-MSCs 后脊髓组织的转录组特征。与注射 VCAM-1 hUC-MSCs 的小鼠相比,VCAM-1 小鼠的临床表现进一步缓解,特别是炎症浸润和活性神经胶质细胞。所有组的小鼠在总体基因表达谱和体细胞突变谱方面均保持保守。EAE 小鼠和 hUC-MSCs 输注小鼠之间差异表达的基因(DEGs)主要参与神经炎症和炎症反应。我们的研究结果表明 VCAM-1 hUC-MSCs 治疗多发性硬化症的可行性,为未来新型 VCAM-1 MSCs 为基础的细胞治疗提供了新的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/02cc45a99580/11064_2024_4267_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/52c1a53390b6/11064_2024_4267_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/a2a565e4b511/11064_2024_4267_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/392808895ddd/11064_2024_4267_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/fee34730add4/11064_2024_4267_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/39e863d6f2be/11064_2024_4267_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/02cc45a99580/11064_2024_4267_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/52c1a53390b6/11064_2024_4267_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/a2a565e4b511/11064_2024_4267_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/392808895ddd/11064_2024_4267_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/fee34730add4/11064_2024_4267_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/39e863d6f2be/11064_2024_4267_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/527d/11607028/02cc45a99580/11064_2024_4267_Fig6_HTML.jpg

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本文引用的文献

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Astragalus polysaccharides promote neural stem cells-derived oligodendrogenesis through attenuating CD8T cell infiltration in experimental autoimmune encephalomyelitis.黄芪多糖通过减轻实验性自身免疫性脑脊髓炎中 CD8T 细胞浸润促进神经干细胞源性少突胶质细胞分化。
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Multiple sclerosis.
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VCAM-1 hUC-MSCs Exert Considerable Neuroprotection Against Cerebral Infarction in Rats by Suppression of NLRP3-Induced Pyroptosis.VCAM-1 修饰的人脐带来源间充质干细胞通过抑制 NLRP3 诱导的焦亡对大鼠脑梗死发挥显著神经保护作用。
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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting.多发性硬化症:神经免疫相互作用和治疗靶点。
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Spatio-temporal metabolokinetics and therapeutic effect of CD106 mesenchymal stem/stromal cells upon mice with acute lung injury.CD106 间质干细胞/基质细胞对急性肺损伤小鼠的时空代谢动力学和治疗效果。
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