期刊
BIOMATERIALS
卷 32, 期 26, 页码 5994-6005出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.05.009
关键词
Acute hepatic failure; Induced pluripotent stem cell; Reactive oxygen species; Hepatocytes
资金
- National Science Council [NSC99-2314-B-075-005-MY3/98-2314-B-075-032-MY3]
- Taipei Veterans General Hospital [98-C1-099/E1-003/ER3-001]
- Yuan-Shan Veteran Hospital [YSVH-9902]
- VGHUST [98-G6-6: 98-P1-01]
- Yen-Tjing-Ling Medical Foundation
- National Yang-Ming University, Ministry of Education, Taiwan
Induced pluripotent stem cells (iPSCs) with four reprogramming factors (Oct-4/Sox2/Klf-4/c-Myc) have been shown to differentiate into hepatic lineages. However, it was unclear whether obviation of the c-Myc oncogene in iPSCs affected hepatic differentiation or inhibited in vivo tumor formation. In this study, we demonstrated that iPSCs without c-Myc had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) with biological functions. As detected using planar-radionuclide imaging and Hoechst labeling assays, these iPSCs and iPSC-Heps tended to mobilize to the injured liver area in thioacetamide (TAA)-treated mice. Intravenous transplantation of both iPSCs and iPSC-Heps but not mouse embryonic fibroblasts (MEFs) reduced the hepatic necrotic area, improved liver functions, and rescued TAA-treated mice from lethal acute hepatic failure (AHF). In addition, microarray-based bioinformatics and quantitative RT-PCR showed high expression of antioxidant genes in iPSCs and iPSC-Heps compared to MEFs. In vivo and in vitro studies of NAC pretreatment confirmed that iPSCs and iPSC-Heps potentially suppressed ROS production and activated antioxidant enzymes in TAA-injured livers. Six months after transplantation in TAA-treated mice, tumor formation was not seen in non-c-Myc iPSC grafts. Therefore, reprogramming adult somatic cells without c-Myc may prevent oxidative stress-induced damage and provide a safer alternative for hepatic regeneration in AHF. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据