Improvement of carbon tetrachloride-induced acute hepatic failure by transplantation of induced pluripotent stem cells without reprogramming factor c-Myc.
Improvement of carbon tetrachloride-induced acute hepatic failure by transplantation of induced pluripotent stem cells without reprogramming factor c-Myc.
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DOI：
10.3390/ijms13033598
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发表时间：
2012
影响因子：
5.6
通讯作者：
Huo TI
中科院分区：
文献类型：
--
作者：
Chang HM;Liao YW;Chiang CH;Chen YJ;Lai YH;Chang YL;Chen HL;Jeng SY;Hsieh JH;Peng CH;Li HY;Chien Y;Chen SY;Chen LK;Huo TI
肝衰竭的唯一治愈性治疗是肝移植。不幸的是，这种治疗有几个主要的局限性，例如供体器官短缺。先前的报道表明，移植诱导多能干细胞而不使用重编程因子c-Myc（3基因iPSC）减弱硫代乙酰胺诱导的肝衰竭，具有最小的致瘤性发生率。在这项研究中，我们研究了3基因iPSC移植是否能够挽救小鼠中四氯化碳（CCl 4）诱导的暴发性肝衰竭和肝性脑病。首先，我们证明了3基因iPSC具有分化为肝细胞样细胞（iPSC-Heps）的能力，所述肝细胞样细胞表现出生物学功能并表达各种肝脏特异性标志物。3-基因iPSC还表现出几种抗氧化酶，防止CCl 4诱导的活性氧产生和细胞死亡。腹腔内移植3-基因iPSC或3-基因iPSC-Heps显著减少CCl 4处理的小鼠的肝坏死面积，改善肝功能和存活率。CCl 4诱导的肝性脑病也通过3基因iPSC移植得到改善。Hoechst染色证实了3-基因iPSC和3-基因iPSC-Heps的成功植入，表明这些细胞的归巢特性。iPSC最明显的肝保护作用似乎源于所有移植细胞中3基因iPSC的最高抗氧化活性。总之，我们的研究结果表明，3基因iPSC可作为治疗急性肝病实验模型的可用细胞来源。
The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases.
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肝组织工程：从移植到实验室定制的基于细胞的肝脏定向疗法。
影响因子：
5.3
作者：
Fiegel HC;Kaufmann PM;Bruns H;Kluth D;Horch RE;Vacanti JP;Kneser U
通讯作者：
Kneser U
影响因子：
14
作者：
Li, Hsin-Yang;Chien, Yueh;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
13.5
作者：
Heo, Jeonghoon;Factor, Valentina M.;Thorgeirsson, Snorri S.
通讯作者：
Thorgeirsson, Snorri S.
影响因子：
0.9
作者：
Abul, H;Mathew, TC;Al-Bader, A
通讯作者：
Al-Bader, A
影响因子：
13.5
作者：
RIBEIRO, J;NORDLINGER, B;PANIS, Y
通讯作者：
PANIS, Y