Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model.
Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model.
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DOI：
10.1371/journal.pone.0019195
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Kobayashi E
中科院分区：
文献类型：
--
作者：
Kanazawa H;Fujimoto Y;Teratani T;Iwasaki J;Kasahara N;Negishi K;Tsuruyama T;Uemoto S;Kobayashi E
与活体肝移植相关的缺血再灌注（I/R）损伤损害了肝移植物的再生。骨髓间充质干细胞（MSC）是肝脏疾病的潜在细胞治疗靶点。在这项研究中，我们证明了骨髓间充质干细胞对肝I/R损伤和肝切除术的影响。我们使用了一种新的大鼠模型，其中进行了大部分肝切除术与I/R损伤。将雄性刘易斯大鼠分为两组：MSC组在再灌注后给予MSC作为治疗，对照组在再灌注后给予磷酸盐缓冲盐水作为安慰剂。观察肝功能、肝组织病理学改变及残肝再生率。通过体内发光成像检查了在表达端粒酶的大鼠中移植的MSC的命运。MSC组在再灌注后24 h出现移植MSC在残肝中荧光素酶活性的高峰，此后荧光素酶活性逐渐下降。MSC注射显著降低血清丙氨酸转氨酶水平的升高。组织学结果显示，与对照组相比，MSC组的空泡变化较低。此外，与对照组相比，在MSC组中观察到TUNEL阳性细胞的百分比显著降低。MSC组的残肝再生速度加快。这些数据表明，MSC移植通过抑制肝细胞凋亡和刺激再生为I/R损伤的肝脏提供营养支持。
Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy. We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group. These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration.
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