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

Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis.
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生物膜填充间充质干细胞通过改善线粒体相关细胞凋亡来治疗急性肾脏疾病。

DOI:
10.1038/srep41136
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发表时间:
2017-01-24
期刊:
影响因子:
4.6
通讯作者:
Wu D
Wu D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Geng X;Hong Q;Wang W;Zheng W;Li O;Cai G;Chen X;Wu D

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横纹肌溶解症诱导的阿基的死亡率仍然很高,因为没有有效的治疗方法。我们研究了一种新的治疗方法,使用MSC。本研究的目的是研究MSC在体内和体外治疗甘油诱导的阿基中的治疗潜力和抗凋亡作用机制。我们用Duragen作为生物膜,将MSCs包裹在甘油损伤的肾组织上。探讨其抗凋亡机制。在体外,HK-2细胞与亚铁肌红蛋白和MSC条件培养基孵育,然后进行细胞增殖和凋亡测定。我们发现,在甘油诱导的阿基小鼠中,在损伤的肾组织上包装MSC可以保护肾功能,改善肾小管病变,并减少细胞凋亡。MSC条件培养液能提高HK-2细胞活力,抑制细胞凋亡。这些作用被PI 3 K抑制剂LY 294002逆转。骨髓间充质干细胞生物膜包裹在肾组织上,通过抑制体内细胞凋亡,具有治疗性拯救作用。骨髓间充质干细胞对肌红蛋白诱导的肾细胞凋亡的保护作用。因此,我们已经证明MSC通过激活PI 3 K/Akt通路和抑制细胞凋亡来减少横纹肌溶解相关的肾损伤和细胞凋亡。
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.