VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury

被引:78
作者
Yuan, Li [1 ,2 ]
Wu, Min-Juan [3 ,4 ]
Sun, Hong-Yu [3 ,4 ]
Xiong, Jun [3 ,4 ]
Zhang, Yi [1 ]
Liu, Chun-Yan [1 ]
Fu, Li-Li [1 ]
Liu, Dong-Mei [1 ]
Liu, Hou-Qi [3 ,4 ]
Mei, Chang-Lin [1 ]
机构
[1] Second Mil Med Univ, Div Nephrol, Changzheng Hosp, Shanghai 20003, Peoples R China
[2] Nantong Univ, Div Nephrol, Affiliated Hosp, Nantong, Jiangsu, Peoples R China
[3] Second Mil Med Univ, Res Ctr Dev Biol, Shanghai 20003, Peoples R China
[4] Second Mil Med Univ, Dept Histol & Embryol, Shanghai 20003, Peoples R China
关键词
vascular endothelial growth factor; ENDOTHELIAL GROWTH-FACTOR; ACUTE-RENAL-FAILURE; MARROW STROMAL CELLS; CYTOKINE EXPRESSION; RECOVERY; SURVIVAL; THERAPY; DISEASE;
D O I
10.1152/ajprenal.00073.2010
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Yuan L, Wu MJ, Sun HY, Xiong J, Zhang Y, Liu CY, Fu LL, Liu DM, Liu HQ, Mei CL. VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury. Am J Physiol Renal Physiol 300: F207-F218, 2011. First published October 13, 2010; doi:10.1152/ajprenal.00073.2010.-The implantation of mesenchymal stem cells (MSC) has been reported as a new technique to restore renal tubular structure and improve renal function in acute kidney injury (AKI). Vascular endothelial growth factor (VEGF) plays an important role in the renoprotective function of MSC. Whether upregulation of VEGF by a combination of MSC and VEGF gene transfer could enhance the protective effect of MSC in AKI is not clear. We investigated the effects of VEGF-modified human embryonic MSC (VEGF-hMSC) in healing cisplatin-injured renal tubular epithelial cells (TCMK-1) with a coculture system. We found that TCMK-1 viability declined 3 days after cisplatin pretreatment and that coculture with VEGF-hMSC enhanced cell protection via mitogenic and antiapoptotic actions. In addition, administration of VEGF-hMSC in a nude mouse model of cisplatin-induced kidney injury offered better protective effects on renal function, tubular structure, and survival as represented by increased cell proliferation, decreased cellular apoptosis, and improved peritubular capillary density. These data suggest that VEGF-modified hMSC implantation could provide advanced benefits in the protection against AKI by increasing antiapoptosis effects and improving microcirculation and cell proliferation.
引用
收藏
页码:F207 / F218
页数:12
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