Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis
Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis
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DOI：
10.3760/cma.j.issn.0366-6999.20130045
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发表时间：
2013-05-20
影响因子：
6.1
通讯作者：
Zhang Jie
中科院分区：
文献类型：
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作者：
Bai Zhi-ming;Deng Xiang-dong;Zhang Jie
背景慢性肾脏病（chronic kidney disease，CDK）是一个世界性的健康问题，但目前还没有完全治愈该病的有效治疗方法。近年来，间充质干细胞（MSCs）治疗各种肾脏疾病的研究取得了突破性进展。方法36只Balb/c小鼠随机分为UUO组、UUO-MSC组和假手术组，每组12只。用慢病毒载体感染MSC，稳定表达荧光素酶报告基因和绿色荧光蛋白基因（Luc-GFP-MSC）。在移植后1、3、14和28天使用体内成像系统（IVIS）追踪MSC的归巢。通过在荧光显微镜下检测冷冻切片中的GFP表达来验证成像结果。结果移植后第3天Luc-GFP-MSCs荧光素酶的表达明显增加，移植后第1周和第4周各组E-cadherin、alpha-SMA、TGF-β 1和TNF-α mRNA的表达均明显增加。移植后7 d开始表达减弱，14 d时表达消失。定量PCR结果显示，UUO组和UUO-MSC组1周时各基因表达无统计学差异，4周时，除TGF-β表达无统计学差异（P>0.05）外，E-cadherin、α-SMA、TNF-α表达在两组间均有统计学差异（P
Background Chronic kidney disease (CDK) is a worldwide health problem, but there is currently no effective treatment that can completely cure this disease. Recently, studies with mesenchymal stem cells (MSCs) on treating various renal diseases have shown breakthroughs. This study is to observe the homing features of MSCs transplanted via kidney artery and effects on renal fibrosis in a reversible unilateral ureteral obstruction (R-UUO) model.Methods Thirty-six Balb/c mice were divided into UUO group, UUO-MSC group, and sham group randomly, with 12 mice in each group. The MSCs had been infected by a lentiviral vector to express stably the luciferase reporter gene and green fluorescence protein genes (Luc-GFP-MSC). Homing of MSCs was tracked using in vivo imaging system (IVIS) 1, 3, 14, and 28 days after transplantation. Imaging results were verified by detecting GFP expression in frozen section under a fluorescence microscope. E-cadherin, alpha-SMA, TGF-beta 1, and TNF-alpha nnRNA expression in all groups at 1 and 4 weeks after transplantation were analyzed by quantitative PCR.Results Transplanted Luc-GFP-MSCs showed increased Luciferase expression 3 days after transplantation. The expression decreased from 7 days, weakened thereafter and could not be detected 14 days after transplantation. Quantitative PCR results showed that all gene expressions in UUO group and UUO-MSC group at 1 week had no statistical difference, while at 4 weeks, except TGF-beta expression (P>0.05), the expression of E-cadherin, alpha-SMA, and TNF-alpha in the above two groups have statistical difference (P