VCAM-1+间充质干细胞/基质细胞在多发性硬化症的实验性自身免疫性脑脊髓炎小鼠模型中显示出比VCAM-1 -对应物更好的疗效

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2024-11-30 DOI:10.1007/s11064-024-04267-w
Haixia Liu, Dongqing Cui, Shasha Huangfu, Xiaojun Wang, Xiao Yu, Hui Yang, Xiaolei Zheng, Yan Li, Jianzhong Bi, Leisheng Zhang, Ping Wang
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引用次数: 0

摘要

尽管基于间充质干细胞/基质细胞(MSCs)的新型干预多发性硬化症(MS)取得了相当大的进展,但VCAM-1 - MSCs和新型VCAM-1+对照物的疾病改善作用在很大程度上尚不清楚。在本研究中,我们利用EAE小鼠模型和VCAM-1+人脐带源性MSCs (hUC-MSCs)来评估系统输注MSCs的治疗效果。一方面,我们通过对脊髓和脑组织的多方面检测,比较了VCAM-1−和VCAM-1+ hUC-MSCs对EAE小鼠的临床症状、脱髓鞘、胶质细胞活性和神经炎症的保护作用。另一方面,我们通过rna测序(RNA-SEQ)和多维生物信息学分析来评估EAE小鼠系统输注hUC-MSCs后脊髓组织的转录组学特征。与注射VCAM-1−hUC-MSCs的小鼠相比,VCAM-1+小鼠的临床表现得到进一步缓解,尤其是炎症浸润和胶质细胞活跃。各组小鼠在总体基因表达谱和体细胞突变谱上均显示出保守性。EAE小鼠与输注hUC-MSCs小鼠的差异表达基因(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用于多发性硬化治疗的可行性,为未来开发新的基于VCAM-1+ mscs的细胞疗法提供新的参考。
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VCAM-1+ Mesenchymal Stem/Stromal Cells Reveal Preferable Efficacy Upon an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis Over the VCAM-1− Counterpart

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.

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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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