High-efficient generation of VCAM-1+mesenchymal stem cells with multidimensional superiorities in signatures and efficacy on aplastic anaemia mice
High-efficient generation of VCAM-1+mesenchymal stem cells with multidimensional superiorities in signatures and efficacy on aplastic anaemia mice
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高效生成VCAM-1( )间充质干细胞，对再生障碍性贫血小鼠具有多维特征和功效优势
DOI：
10.1111/cpr.12862
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发表时间：
2020-06-29
影响因子：
8.5
通讯作者：
Han, Zhongchao
中科院分区：
文献类型：
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作者：
Wei, Yimeng;Zhang, Leisheng;Han, Zhongchao
目的纵向研究表明，VCAM-1(+)间充质干细胞/基质细胞(MSCs)是一种很有前途的再生医学资源，但在优势和“废弃”的Huc-MSCs中基因表达的丰度远远不够。因此，高效的制备和系统地剖析亚群的特征和生物功能是大规模临床应用的前提。材料与方法我们主要利用基于细胞因子的编程策略大规模生成VCAM-1(+)Huc-MSC(III-MSCs)。此后，我们进行了多方面的分析，包括细胞形态、免疫表型、细胞活力、多系分化、全基因组分析、管形成和Matrigel塞法、淋巴细胞激活和分化以及系统移植治疗再生障碍性贫血(AA)。结果IL-1β、IL-4与干扰素-γ相结合可获得高比例表达VCAM-1的III-MSCs，其免疫表型与未处理的Huc-MSCs(NT-MSCs)相似，但在细胞和分子水平上表现出多维优势。同时，全身输注III-MSCs可以显著改善AA小鼠的临床病理特征，最终有助于AA小鼠的造血重建和免疫调节。结论我们建立了一种高效、高效的III-MSCs的大规模制备方法，该方法具有较好的表型和治疗再生障碍性贫血的疗效。我们的研究结果表明，III-MSCs具有多方面的特性，是再生医学的有利来源。
Objective Longitudinal studies have indicated VCAM-1(+)mesenchymal stem/stromal cells (MSCs) as promising resources in regenerative medicine, yet the abundance in gene expression is far from adequate in the advantaged and "discarded" hUC-MSCs. Thus, high-efficient preparation and systematic dissection of the signatures and biofunctions of the subpopulation is the prerequisite for large-scale clinical applications. Materials and methods We primarily took advantage of a cytokine-based programming strategy for large-scale VCAM-1(+)hUC-MSC generation (III-MSCs). Thereafter, we conducted multifaceted analyses including cytomorphology, immunophenotype, cell vitality, multilineage differentiation, whole-genome analysis, tube formation and Matrigel plug assay, lymphocyte activation and differentiation, and systemic transplantation for aplastic anaemia (AA) treatment. Results III-MSCs with high-proportioned VCAM-1 expression were obtained by combining IL-1 beta, IL-4 with IFN-gamma, which exhibited comparable immunophenotype with untreated hUC-MSCs (NT-MSCs) but revealed multidimensional superiorities both at the cellular and molecular levels. Simultaneously, systemic infusion of III-MSCs could significantly ameliorate clinicopathological features and finally help facilitate haematopoietic reconstruction and immunoregulation in AA mice. Conclusions We have established a high-efficient procedure for large-scale generation of III-MSCs with preferable signatures and efficacy upon aplastic anaemia in mice. Our findings suggested that III-MSCs were advantageous sources with multifaceted characteristics for regenerative medicine.