用于肝细胞移植转化研究的猪胚胎干细胞的肝向分化

Hepatic differentiation of porcine embryonic stem cells for translational research of hepatocyte transplantation.

作者信息

Park K M, Hussein K H, Ghim J H, Ahn C, Cha S H, Lee G S, Hong S H, Yang S, Woo H M

机构信息

Stem Cell Institute, Kangwon National University, Chuncheon, Korea; College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea.

Stem Cell Institute, Kangwon National University, Chuncheon, Korea.

出版信息

Transplant Proc. 2015 Apr;47(3):775-9. doi: 10.1016/j.transproceed.2015.01.020.

DOI:10.1016/j.transproceed.2015.01.020

PMID:25891729

Abstract

Porcine embryonic stem cells (ES) are considered attractive preclinical research tools for human liver diseases. Although several studies previously reported generation of porcine ES, none of these studies has described hepatic differentiation from porcine ES. The aim of this study was to generate hepatocytes from porcine ES and analyze their characteristics. We optimized conditions for definitive endoderm induction and developed a 4-step hepatic differentiation protocol. A brief serum-free condition with activin A efficiently induced definitive endoderm differentiation from porcine ES. The porcine ES-derived hepatocyte-like cells highly expressed hepatic markers including albumin and α-fetoprotein, and displayed liver characteristics such as glycogen storage, lipid production, and low-density lipoprotein uptake. For the first time, we describe a highly efficient protocol for hepatic differentiation from porcine ES. Our findings provide valuable information for translational liver research using porcine models, including hepatic regeneration and transplant studies, drug screening, and toxicology.

摘要

猪胚胎干细胞（ES）被认为是用于人类肝脏疾病的有吸引力的临床前研究工具。尽管此前有几项研究报道了猪ES细胞的产生，但这些研究均未描述猪ES细胞向肝细胞的分化。本研究的目的是从猪ES细胞中生成肝细胞并分析其特性。我们优化了确定内胚层诱导的条件，并开发了一种4步肝分化方案。使用激活素A的短暂无血清条件可有效诱导猪ES细胞向确定内胚层分化。猪ES细胞来源的类肝细胞高表达包括白蛋白和甲胎蛋白在内的肝脏标志物，并表现出糖原储存、脂质产生和低密度脂蛋白摄取等肝脏特性。我们首次描述了一种从猪ES细胞高效分化为肝细胞的方案。我们的研究结果为使用猪模型进行转化性肝脏研究提供了有价值的信息，包括肝脏再生和移植研究、药物筛选以及毒理学研究。