Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology
文献类型：期刊论文
| 作者 | Wu, Zhi-Tao1; Yao, Dan1; Ji, Shu-Yi2; Ni, Xuan1; Gao, Yi-Meng2; Hui, Li-Jian2; Pan, Guo-Yu1
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| 刊名 | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
 |
| 出版日期 | 2016 |
| 卷号 | 38期号:5页码:1815-1830 |
| 关键词 | Direct reprogramming Hepatocyte-like cells Hepatic transporters Biliary clearances Cholestasis |
| ISSN号 | 1015-8987 |
| DOI | 10.1159/000443120 |
| 文献子类 | Article |
| 英文摘要 | Background/Aims: To develop a suitable hepatocyte-like cell model that could be a substitute for primary hepatocytes with essential transporter expression and functions. Induced hepatocyte-like (iHep) cells directly reprogrammed from mice fibroblast cells were fully characterized. Methods: Nave iHep cells were transfected with nuclear hepatocyte factor 4 alpha (Hnf4 alpha) and treated with selected small molecules. Sandwich cultured configuration was applied. The mRNA and protein expression of transporters were determined by Real Time PCR and confocal. The functional transporters were estimated by drug biliary excretion measurement. The inhibition of bile acid efflux transporters by cholestatic drugs were assessed. Results: The expression and function of p-glycoprotein (P-gp), bile salt efflux pump (Bsep), multidrug resistance-associated protein 2 (Mrp2), Na+-dependent taurocholate cotransporting polypeptide (Ntcp), and organic anion transporter polypedtides (Oatps) in iHep cells were significantly improved after transfection of hepatocyte nuclear factor 4 alpha (Hnf4a) and treatment with selected inducers. in vitro intrinsic biliary clearances (CLb,int) of optimized iHep cells for rosuvastatin, methotrexate, d8-TCA (deuterium-labeled sodium taurocholate acid) and DPDPE ([D-Pen(2,5)] enkephalin hydrate) correlated well with that of sandwich-cultured primary mouse hepatocytes (SCMHs) (r(2) = 0.984). Cholestatic drugs were evaluated and the results were compared well with primary mice hepatocytes. Conclusion: The optimized iHep cells expressed functional drug transporters and were comparable to primary mice hepatocytes. This study suggested direct reprogramming could provide a potential alternative to primary hepatocytes for drug candidate hepatobiliary disposition and hepatotoxicity screening. Copyright (C) 2016 S. Karger AG, Basel |
| WOS关键词 | SALT EXPORT PUMP ; BILE-ACID TRANSPORTERS ; SANDWICH-CULTURED RAT ; EMBRYONIC STEM-CELLS ; DEFINED FACTORS ; HEPATIC DIFFERENTIATION ; DIRECT CONVERSION ; SMALL MOLECULES ; LIVER ; METABOLISM |
| 资助项目 | National Natural Science Foundation of China[81302836] ; National Natural Science Foundation of China[81573499] ; National High Technology Research and Development Program of China[2013AA032202] |
| WOS研究方向 | Cell Biology ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000375787800015 |
| 出版者 | KARGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276229]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Pan, Guo-Yu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Haike Rd 501, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Zhi-Tao,Yao, Dan,Ji, Shu-Yi,et al. Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology[J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,2016,38(5):1815-1830. |
| APA | Wu, Zhi-Tao.,Yao, Dan.,Ji, Shu-Yi.,Ni, Xuan.,Gao, Yi-Meng.,...&Pan, Guo-Yu.(2016).Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,38(5),1815-1830. |
| MLA | Wu, Zhi-Tao,et al."Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 38.5(2016):1815-1830. |
入库方式： OAI收割
来源：上海药物研究所
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