Cao Zhiqiang, Zhang Geng, Wang Fuli, Liu Hongbao, Liu Long, Han Yaling, Zhang Jian, Yuan Jianlin
Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
PLoS One. 2013 Dec 30;8(12):e82949. doi: 10.1371/journal.pone.0082949. eCollection 2013.
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.
间充质干细胞归巢至损伤组织对纠正诸如缺血再灌注损伤（IRI）和免疫损伤等病症很重要，此前已有相关研究，但效率较低。为了从间充质干细胞移植中获得临床益处，需要大幅提高其植入效率。趋化因子是控制细胞迁移的最重要因素。基质细胞衍生因子-1（SDF-1）在组织/器官缺血损伤时上调，其同源受体趋化因子受体4（CXCR4）参与干细胞迁移。我们研究的目的是调查间充质干细胞中CXCR4的表达，并验证其在介导向移植肾迁移中的作用及其在肾脏保护中的免疫调节作用。具体而言，本研究旨在调查携带基因修饰CXCR4的间充质干细胞在大鼠肾移植模型中的短期组织归巢情况。我们检验了CXCR4过表达的间充质干细胞能更有效地调节免疫反应这一假设。慢病毒载体用于在大鼠间充质干细胞中过表达CXCR4或引入靶向内源性CXCR4的短发夹核糖核酸（shRNA）构建体。间充质干细胞用增强型绿色荧光蛋白（eGFP）标记。细胞分选后，对受体肾脏进行区域灌注；肾移植后，经尾静脉给受体动物注射转导的间充质干细胞、天然间充质干细胞或磷酸盐缓冲液（PBS）；并观察间充质干细胞注射的效果。
