人端粒酶反转录酶基因修饰脐带间充质干细胞移植治疗急性肾损伤

Human telomerase reverse transcriptase gene-modified umbilical cord mesenchymal stem cell transplantation for acute kidney injury

背景:人端粒酶反转录酶(hTERT)是调控增殖及定向分化的首选生长因子之一,具有多重生物学效应,为建立基因工程的永生化干细胞系奠定了基础。目的:探讨人端粒酶反转录酶基因修饰脐带间充质干细胞移植对大鼠缺血再灌注诱导的急性肾损伤的治疗作用。方法:体外培养人脐带间充质干细胞,构建缺血再灌注诱导的大鼠急性肾损伤模型,建模后将大鼠随机分为3组:对照组尾静脉注射1 mL L-DMEM培养液;空载病毒组:尾静脉注射1 m L经空载病毒转染人脐带间充质干细胞悬液;hT ERT转染组尾静脉注射1 mL经PLXSN-hT ERT转染的人脐带间充质干细胞悬液。结果与结论:移植后第3,28天苏木精-伊红染色检查示hT ERT转染组的肾小管损伤评分<空载病毒组<对照组(P<0.05)。移植后第28天,CM-Dil阳性细胞数为hT ERT转染组>空载病毒组>对照组(P<0.05)。移植细胞后第1,3,14,28天血肌酐、尿素氮水平均为hT ERT转染组<空载病毒组<对照组(P<0.05)。结果证实,hT ERT基因修饰脐带间充质干细胞移植对大鼠急性肾损伤具有明显的修复作用。

BACKGROUND：The human telomerase reverse transcriptase（hT ERT） is one of preferred growth factors for regulating proliferation and directional differentiation,has multiple biological effects,and laids the foundation for genetically engineered immortalized stem cell lines.OBJECTIVE： To investigate the effect of hT ERT gene-modified umbilical cord mesenchymal stem cell transplantation on acute kidney injury induced by ischemia and reperfusion in rats.METHODS： The human umbilical cord mesenchymal stem cells were cultured in vitro. Rat models of acute kidney injury induced by ischemia and reperfusion were established. Rat models were randomly divided into three groups Rats in the control group were injected with 1 m L L-DMEM medium through caudal vein. Rats in the negative transfection group were injected with 1 mL umbilical cord mesenchymal stem cell suspension after empty virus transfection through caudal vein. Rats in the hT ERT transfection group were injected with 1 m L umbilical cord mesenchymal stem cell suspension after PLXSN-hT ERT transfection through caudal vein.RESULTS AND CONCLUSION： At 3 and 28 days after transplantation,hematoxylin-eosin staining showed renal tubular damage score in the hT ERT transfection group negative transfection group control group（P〈0.05）. At28 days after transplantation,the number of CM-Dil-positive cells in the hT ERT transfection group negative transfection group control group（P〈0.05）. At 1,3,14,and 28 days,serum creatinine and urea nitrogen levels in the hT ERT transfection group negative transfection group control group（P〈0.05）. The results confirm that hTERT gene-modified umbilical cord mesenchymal stem cell transplantation has a significant repair effect on acute kidney injury in rats.