Protective effects of mesenchymal stem cells with CXCR4 up-regulation in a rat renal transplantation model.
Protective effects of mesenchymal stem cells with CXCR4 up-regulation in a rat renal transplantation model.
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DOI：
10.1371/journal.pone.0082949
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Cao Z;Zhang G;Wang F;Liu H;Liu L;Han Y;Zhang J;Yuan J
间充质干细胞在损伤组织内的归巢对于修复缺血再灌注损伤（IRI）和免疫损伤等疾病具有重要意义，此前已有研究，但效率较低。骨髓间充质干细胞移植的临床获益需要在植入方面有实质性的改进。趋化因子是控制细胞迁移的最重要因素。基质衍生因子-1 （SDF-1）在组织/器官缺血损伤过程中表达上调，其同源受体趋化因子受体4 （CXCR4）参与干细胞迁移。我们的研究目的是研究CXCR4在MSCs中的表达，并验证其介导移植肾迁移的作用及其在肾保护中的免疫调节作用。具体来说，本研究旨在研究携带转基因CXCR4的间充质干细胞在大鼠肾移植模型中的短期组织归巢。我们验证了CXCR4过表达的MSCs可以更有效地调节免疫反应的假设。在大鼠间充质干细胞中，使用慢病毒载体过表达CXCR4或引入针对内源性CXCR4的短发夹核糖核酸（shRNA）构建物。用增强的绿色荧光蛋白（eGFP）标记MSCs。细胞分选后，局部灌注受体肾；受体动物在肾移植后通过尾静脉注射转导的间充质干细胞、天然间充质干细胞或PBS；观察骨髓间充质干细胞注射的作用。
The homing of mesenchymal stem cells to injured tissue, which is important for the correction of conditions such as ischemia-reperfusion injury (IRI) and immunolesions, has been performed previously, but with poor efficiency. Substantial improvements in engraftment are required to derive clinical benefits from MSC transplantation. Chemokines are the most important factors that control cellular migration. Stromal derived factor-1 (SDF-1) is up-regulated during tissue/organ ischemia damage, and its cognate receptor, chemokine receptor 4 (CXCR4), is involved in stem cell migration. The aim of our study was to investigate CXCR4 expression in MSCs and to validate both its role in mediating migration to transplanted kidneys and its immunoregulatory effects in renal protection. Specifically, the present study was designed to investigate the short-term tissue homing of MSCs carrying genetically modified CXCR4 in a rat renal transplantation model. We tested the hypothesis that MSCs with CXCR4 over-expression can more efficiently regulate immunological reactions. Lentiviral vectors were used to over-express CXCR4 or to introduce a short hairpin ribonucleic acid (shRNA) construct targeting endogenous CXCR4 in rat MSCs. MSCs were labeled with enhanced green fluorescent protein (eGFP). After cell sorting, recipient kidneys were regionally perfused; recipient animals were injected with transduced MSCs, native MSCs, or PBS via tail vein following renal transplantation; and the effects of MSC injection were observed.
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影响因子：
0.9
作者：
De Martino, M.;Zonta, S.;Alessiani, M.
通讯作者：
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影响因子：
4.4
作者：
English, Karen;Barry, Frank P.;Mahon, Bernard P.
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DOI：
10.1152/ajprenal.00451.2009
发表时间：
2010-01-01
影响因子：
4.2
作者：
Gupta, Sandeep;Li, Shunan;Rosenberg, Mark
通讯作者：
Rosenberg, Mark
影响因子：
4
作者：
Gheisari, Yousof;Azadmanesh, Kayhan;Zeinali, Sirous
通讯作者：
Zeinali, Sirous