首页> 外文期刊>Tissue engineering, Part C. Methods >Lineage restriction and differentiation of human embryonic stem cells into hepatic progenitors and zone 1 hepatocytes.
【24h】

Lineage restriction and differentiation of human embryonic stem cells into hepatic progenitors and zone 1 hepatocytes.

机译:人类胚胎干细胞的谱系限制和分化为肝祖细胞和1区肝细胞。

获取原文
获取原文并翻译 | 示例
           

摘要

Human embryonic stem (hES) cells can self-renew, which enables them to have considerable expansion potential, and are pluripotent. If their differentiation can be controlled, they can offer promise for clinical programs in cell therapies. A novel strategy has been developed to derive early hepatocytic lineage stages from hES cells using four sequential inducing steps lasting 16 days. First, embryoid bodies (EBs) were generated by growing hES cells in suspension for 2 days; second, EBs were lineage restricted to definitive endoderm with 3 days of treatment with human activin A; third, cells were differentiated further by coculturing for 5 days with human fetal liver stromal cells (hFLSCs) made transgenic to stably release basic fibroblast growth factor (bFGF); fourth, treating them for 6 days with soluble signals comprised of hFLSC-derived bFGF, hepatocyte growth factor, oncostatin M, and dexamethasone. Induced cells displayed morphological, immunohistochemical, and biochemical characteristics of hepatocytic committed progenitors and of early lineage stage hepatocytes found in zone 1 of the liver acinus. They expressed alpha-fetoprotein, albumin, cytokeratin 18, glycogen, a fetal P450 isoform, and CYP1B1, and demonstrated indocyanine green uptake and excretion. In conclusion, we have developed a novel method to lineage restrict hES cells into early lineage stages of hepatocytic fates.
机译:人类胚胎干(hES)细胞可以自我更新,从而使其具有相当大的扩增潜力,并且具有多能性。如果可以控制它们的分化,那么它们可以为细胞疗法的临床计划提供希望。已经开发出一种新颖的策略,可以使用持续16天的四个连续诱导步骤从hES细胞获得早期肝细胞谱系阶段。首先,通过在悬浮状态下培养hES细胞2天来产生胚状体(EBs);其次,用人类激活素A治疗3天后,EB只能在定形内胚层中谱系;第三,通过与转基因以稳定释放碱性成纤维细胞生长因子(bFGF)的人胎肝基质细胞(hFLSC)共培养5天,进一步分化细胞。第四,用可溶信号处理6天,这些信号包括hFLSC衍生的bFGF,肝细胞生长因子,制瘤素M和地塞米松。诱导的细胞显示出在肝腺泡1区发现的肝细胞定型祖细胞和早期谱系阶段肝细胞的形态,免疫组织化学和生化特征。他们表达了甲胎蛋白,白蛋白,细胞角蛋白18,糖原,胎儿P450亚型和CYP1B1,并证明了吲哚菁绿的摄取和排泄。总之,我们已经开发出一种新的方法来沿谱系限制hES细胞进入肝细胞命运的早期谱系阶段。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号