Hepatocyte Growth Factor Modification Promotes the Amelioration Effects of Human Umbilical Cord Mesenchymal Stem Cells on Rat Acute Kidney Injury

被引：85

作者：

Chen, Yuan ^{[1
]}

Qian, Hui ^{[1
]}

Zhu, Wei ^{[1
]}

Zhang, Xu ^{[1
]}

Yan, Yongmin ^{[1
]}

Ye, Shengqin ^{[2
]}

Peng, Xiujuan ^{[1
]}

Li, Wei ^{[2
]}

Xu, Wenrong ^{[1
]}

机构：

[1] Jiangsu Univ, Sch Med Sci & Lab Med, Zhenjiang 212013, Jiangsu, Peoples R China

[2] Jiangsu Ctr Stem Cell Engn & Technol, China Med City, Taizhou, Peoples R China

来源：

STEM CELLS AND DEVELOPMENT | 2011年 / 20卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ACUTE-RENAL-FAILURE; ISCHEMIA-REPERFUSION INJURY; IN-VITRO; RECOVERY; INFLAMMATION; INHIBITION; APOPTOSIS; CD44; MICE; MET;

D O I：

10.1089/scd.2009.0495

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are particularly attractive cells for cellular and gene therapy in acute kidney injury (AKI). Adenovirus-mediated gene therapy has been limited by immune reaction and target genes selection. However, in the present study, we investigated the therapeutic effects of hepatocyte growth factor modified hucMSCs (HGF-hucMSCs) in ischemia/reperfusion-induced AKI rat models. In vivo animal models were generated by subjecting to 60 min of bilateral renal injury by clamping the renal pedicles and then introduced HGF-hucMSCs via the left carotid artery. Our results revealed that serum creatinine and urea nitrogen levels decreased to the baseline more quickly in HGF-hucMSCs-treated group than that in hucMSCs- or green fluorescent protein-hucMSCs-treated groups at 72 h after injury. The percent of proliferating cell nuclear antigen-positive cells in HGF-hucMSCs-treated group was higher than that in the hucMSCs or green fluorescent protein-hucMSCs-treated groups. Moreover, injured renal tissues treated with HGF-hucMSCs also exhibited less hyperemia and renal tubule cast during the recovery process. Immunohistochemistry and living body imaging confirmed that HGF-hucMSCs localize to areas of renal injury. Real-time polymerase chain reaction result showed that HGF-hucMSCs also inhibited caspase-3 and interleukin-1 beta mRNA expression in injured renal tissues. Western blot also showed HGF-hucMSCs-treated groups had lower expression of interleukin-1 beta. Terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate (dUTP) nick end labeling method indicated that HGF-hucMSCs-treated group had the least apoptosis cells. In conclusion, our findings suggest that HGF modification promotes the amelioration of ischemia/reperfusion-induced rat renal injury via antiapoptotic and anti-inflammatory mechanisms; thus, providing a novel therapeutic application for hucMSCs in AKI.

引用

页码：103 / 113

页数：11

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