Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis

被引:35
作者
Geng, Xiaodong [1 ]
Hong, Quan [1 ]
Wang, Weiwei [2 ,3 ]
Zheng, Wei [1 ]
Li, Ou [1 ]
Cai, Guangyan [1 ]
Chen, Xiangmei [1 ]
Wu, Di [1 ]
机构
[1] Peoples Liberat Army Gen Hosp, Beijing Key Lab Kidney Dis, State Key Lab Kidney Dis, Natl Clin Res Ctr Kidney Dis,Dept Nephrol,Inst Ne, 28 Fuxing Rd, Beijing 100853, Peoples R China
[2] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Thorac Surg, 1 Shuai Fu Yuan, Beijing 100730, Peoples R China
[3] Peking Union Med Coll, 1 Shuai Fu Yuan, Beijing 100730, Peoples R China
基金
国家高技术研究发展计划(863计划);
关键词
INJURY; MECHANISMS; ACTIVATION; PATHWAYS; H2O2;
D O I
10.1038/srep41136
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mortality of rhabdomyolysis-induced AKI remains high because no effective therapy exists. We investigated a new therapeutic method using MSCs. The aim of this study was to investigate the therapeutic potential and anti-apoptotic mechanisms of action of MSCs in the treatment of AKI induced by glycerol in vivo and in vitro. We used Duragen as a biological membrane to pack MSCs on the glycerol-injured renal tissue in vivo. The anti-apoptotic mechanism was investigated. In vitro, HK-2 cells were incubated with ferrous myoglobin and MSCs-conditioned medium, followed by cell proliferation and apoptosis assays. We founded that packing MSCs on the injured renal tissue preserved renal function, ameliorated renal tubular lesions, and reduced apoptosis in the mice with glycerol-induced AKI. The MSC-conditioned medium improved HK-2 cell viability and inhibited apoptosis. These effects were reversed by the PI3K inhibitor LY294002. Biological membrane packing of MSCs on the renal tissue has a therapeutic rescue function by inhibiting cell apoptosis in vivo. MSCs protect renal cells from apoptosis induced by myoglobin in vitro. We have thus demonstrated MSCs reduced rhabdomyolysis-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway and inhibiting apoptosis.
引用
收藏
页数:12
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