Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes.
Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes.
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发表时间：
2002-07
影响因子：
4
通讯作者：
H. Malhi;A. Irani;S. Gagandeep;Sanjeev Gupta
中科院分区：
文献类型：
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作者：
H. Malhi;A. Irani;S. Gagandeep;Sanjeev Gupta
肝脏可以通过它所拥有的祖细胞进行自我再生。在这里，我们证明了上皮祖细胞/干细胞的分离，从胎儿人肝脏，其中含有大量的成肝细胞。祖肝细胞显示克隆形成能力，表达肝细胞，胆管细胞和卵圆细胞中观察到的基因，并纳入腺病毒或慢病毒载体转移的基因。在培养条件下，祖细胞增殖了几个月，每个细胞经历了40多次分裂，但它们保留了正常的核型。在患有严重联合免疫缺陷的小鼠中，无论是在异位位置还是在肝脏本身，祖细胞都分化为成熟的肝细胞。肝损伤后细胞在肝实质中整合并增殖。人胎肝中祖细胞的丰度与表明器官老化和成熟期间祖细胞/干细胞耗竭的模型一致。这些研究表明，从胎儿器官中分离祖细胞将适合于建立新的系统，以研究基本机制以及细胞和基因治疗。
The liver can regenerate itself through the progenitor cells it harbors. Here we demonstrate isolation of epithelial progenitor/stem cells from the fetal human liver, which contains a large number of hepatoblasts. Progenitor liver cells displayed clonogenic capacity, expressed genes observed in hepatocytes, bile duct cells and oval cells, and incorporated genes transferred by adenoviral or lentiviral vectors. Under culture conditions, progenitor cells proliferated for several months, with each cell undergoing more than forty divisions, but they retained normal karyotypes. Progenitor cells differentiated into mature hepatocytes in mice with severe combined immunodeficiency, both when in an ectopic location and when in the liver itself. Cells integrated in the liver parenchyma and proliferated following liver injury. An abundance of progenitor cells in the fetal human liver is consistent with models indicating depletion of progenitor/stem cells during aging and maturation of organs. The studies indicate that isolation of progenitor cells from fetal organs will be appropriate for establishing novel systems to investigate basic mechanisms and for cell and gene therapy.