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小鼠胚胎干细胞在体外分化为具有凝血因子VIII和IX表达谱的肝细胞。

In vitro differentiation of mouse ES cells into hepatocytes with coagulation factors VIII and IX expression profiles.

作者信息

Meng Ying, Huang Shaoliang, Min Jun, Guo Zhongmin

机构信息

Center for Stem Cell Research, the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, China.

出版信息

Sci China C Life Sci. 2006 Jun;49(3):259-64. doi: 10.1007/s11427-006-0259-3.

DOI:10.1007/s11427-006-0259-3
PMID:16856495
Abstract

Coagulation factors II, V, VII, VIII, IX and X are produced by hepatocytes. So factors VIII and IX deficiencies, which result in hemophilia A and B, have the potential to respond to cellular replacement therapy. Embryonic stem (ES) cells provide a unique source for therapeutic applications. Here, E14 mouse ES cells have been induced into hepatocytes in vitro. Morphology revealed that ES-derived hepatic-like cells were round or polyhedral shaped with distinct boundary of individual cells, and some arranged in trabeculae. These cells expressed endodermal- or liver-specific mRNA--transthyretin (TTR), alpha1-anti-trypsin (AAT), alpha-fetoprotein (AFP), albumin (ALB), glucose-6-phoshpatase (G6P) and tyrosine aminotransferase (TAT). Approximately (85.1 +/- 0.5)% of the ES-derived cells was stained positive green with ICG uptake. These cells were also stained magenta as a result of PAS reaction. In this paper, expression of coagulation factors VIII and IX mRNA in the ES-derived cells is documented. Therefore, ES cells might be developed as substitute donor cells for the therapy of coagulation factor deficiencies.

摘要

凝血因子II、V、VII、VIII、IX和X由肝细胞产生。因此,导致甲型和乙型血友病的VIII因子和IX因子缺乏症有可能对细胞替代疗法产生反应。胚胎干细胞(ES细胞)为治疗应用提供了独特的来源。在此,E14小鼠ES细胞已在体外被诱导分化为肝细胞。形态学显示,ES细胞来源的类肝细胞呈圆形或多面体形,单个细胞边界清晰,部分细胞排列成小梁状。这些细胞表达内胚层或肝脏特异性mRNA——转甲状腺素蛋白(TTR)、α1-抗胰蛋白酶(AAT)、甲胎蛋白(AFP)、白蛋白(ALB)、葡萄糖-6-磷酸酶(G6P)和酪氨酸转氨酶(TAT)。约(85.1±0.5)%的ES细胞来源细胞经吲哚菁绿摄取后被染成绿色阳性。这些细胞经PAS反应后也被染成品红色。本文记录了ES细胞来源细胞中凝血因子VIII和IX mRNA的表达情况。因此,ES细胞有可能被开发成为用于治疗凝血因子缺乏症的替代供体细胞。

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In vitro differentiation of mouse ES cells into hepatocytes with coagulation factors VIII and IX expression profiles.小鼠胚胎干细胞在体外分化为具有凝血因子VIII和IX表达谱的肝细胞。
Sci China C Life Sci. 2006 Jun;49(3):259-64. doi: 10.1007/s11427-006-0259-3.
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Generation of an mESC model with a human hemophilia B nonsense mutation via CRISPR/Cas9 technology.通过 CRISPR/Cas9 技术生成携带人血友病 B 无义突变的 mESC 模型。
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