Differentiation and transplantation of human embryonic stem cell-derived hepatocytes.
Differentiation and transplantation of human embryonic stem cell-derived hepatocytes.
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DOI：
10.1053/j.gastro.2008.10.047
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发表时间：
2009-03
期刊：
影响因子：
29.4
通讯作者：
Fox IJ
中科院分区：
文献类型：
--
作者：
Basma H;Soto-Gutiérrez A;Yannam GR;Liu L;Ito R;Yamamoto T;Ellis E;Carson SD;Sato S;Chen Y;Muirhead D;Navarro-Alvarez N;Wong RJ;Roy-Chowdhury J;Platt JL;Mercer DF;Miller JD;Strom SC;Kobayashi N;Fox IJ
获得无限数量的人类肝细胞的能力将促进肝病基于细胞的疗法的发展，促进肝脏生物学的研究，并改善药物发现的早期阶段。胚胎干细胞是多能的，可以分化成任何类型的细胞，因此可以作为人类肝细胞的来源。为了产生人肝细胞，通过在成纤维细胞生长因子2和人激活素-A、肝细胞生长因子和地塞米松中连续培养来分化人胚胎干细胞。通过分选表面去唾液酸糖蛋白受体表达分离功能性肝细胞。通过实时PCR、免疫组织化学、免疫印迹、功能测定和移植进行表征。胚胎干细胞衍生的肝细胞表达肝脏特异性基因，但不表达代表其他谱系的基因，分泌与原代人肝细胞相似的功能性人肝脏特异性蛋白，并表现出人肝细胞色素P450代谢活性。注射胚胎干细胞衍生肝细胞的啮齿动物血清含有大量人血白蛋白和α-1-抗胰蛋白酶。细胞角蛋白-18和人白蛋白表达细胞的菌落存在于受体动物的肝脏中。人胚胎干细胞可以分化为具有原代人肝细胞许多特征的细胞。肝细胞样细胞可以基于脱唾液酸糖蛋白受体表达进行富集和回收，并且可以潜在地用于药物发现研究和开发为治疗剂。
The ability to obtain unlimited numbers of human hepatocytes would improve development of cell-based therapies for liver diseases, facilitate the study of liver biology and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, can potentially differentiate into any cell type and could therefore be developed as a source of human hepatocytes. To generate human hepatocytes, human embryonic stem cells were differentiated by sequential culture in fibroblast growth factor 2 and human Activin-A, hepatocyte growth factor, and dexamethasone. Functional hepatocytes were isolated by sorting for surface asialoglycoprotein receptor expression. Characterization was performed by real-time PCR, imunohistochemistry, immunoblot, functional assays and transplantation. Embryonic stem cell-derived hepatocytes expressed liver-specific genes but not genes representing other lineages, secreted functional human liver-specific proteins similar to those of primary human hepatocytes and demonstrated human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and alpha-1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals. Human embryonic stem cells can be differentiated into cells with many characteristics of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein receptor expression and could potentially be used in drug discovery research and developed as therapeutics.
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影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
5.8
作者：
Ek, Monica;Soderdahl, Therese;Johansson, Inger
通讯作者：
Johansson, Inger
影响因子：
25.7
作者：
Khurana, Satish;Mukhopadhyay, Asok
通讯作者：
Mukhopadhyay, Asok
影响因子：
6
作者：
Laconi, E;Oren, R;Shafritz, DA
通讯作者：
Shafritz, DA
DOI：
10.1073/pnas.92.11.4942
发表时间：
1995-05-23
影响因子：
11.1
作者：
RHIM, JA;SANDGREN, EP;BRINSTER, RL
通讯作者：
BRINSTER, RL