Chiang Chih-Hung, Chang Ching-Chih, Huang Hui-Chun, Chen Yi-Jen, Tsai Ping-Hsing, Jeng Shaw-Yeu, Hung Shuen-Iu, Hsieh Jung-Hung, Huang Hsu-Shan, Chiou Shih-Hwa, Lee Fa-Yauh, Lee Shou-Dong
Institute of Pharmacology, National Yang-Ming University, No. 155 Section 2 Linong Street, Taipei, Taiwan.
J Biomed Biotechnol. 2011;2011:219060. doi: 10.1155/2011/219060. Epub 2011 Jul 26.
To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy.
迄今为止，肝移植是终末期肝病的唯一有效治疗方法。考虑到多能性以及分化为三胚层谱系的潜力，诱导多能干细胞（iPSC）可能成为基于细胞治疗的替代方法。在此，我们研究了iPSC移植对硫代乙酰胺（TAA）诱导的小鼠急性/暴发性肝衰竭（AHF）的影响。首先，我们证明iPSC有能力分化为表达各种肝脏标志物（包括白蛋白、甲胎蛋白和肝细胞核因子-3β）并具有生物学功能的肝样细胞（iPSC-Hep）。iPSC的静脉移植有效减少了肝脏坏死面积，改善了肝功能和运动活性，并将TAA处理的小鼠从致命性AHF中拯救出来。1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐细胞标记显示iPSC可能迁移至受损肝脏区域。综上所述，iPSC可有效挽救实验性AHF，是基于细胞治疗的潜在有利细胞来源。
