Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated hepatoblasts
Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated hepatoblasts
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DOI：
10.1089/ten.a.2007.0131
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Reid, L. M.
中科院分区：
文献类型：
--
作者：
Cheng, Nancy;Wauthier, Eliane;Reid, L. M.
藻酸盐凝胶用于提供包封以支持来自人胎肝的肝祖细胞的生长和最终分化。包封的细胞在培养中几天内聚集成球状体，并在无血清培养基中继续生长至少4周。球状体中的肝祖细胞经历分化，如成熟肝细胞功能的出现所示，如氨解毒、白蛋白分泌、成体细胞色素P450同工酶CYP3A4的表达和CYP2C9的典型酶活性。沿着成熟肝标志物的表达，这些祖细胞失去了未成熟肝细胞的典型特征，如上皮细胞粘附分子。除了获得成熟的生化功能外，球状体还发育了胆管，这表明它们已经分化成类似于完整肝脏中的组织。
Alginate gel was used to provide encapsulation to support the growth and eventually the differentiation of hepatic progenitors cells derived from human fetal livers. The encapsulated cells aggregated into spheroids within a few days in culture and continued to grow for at least 4 weeks in a serum-free medium. The hepatic progenitor cells in the spheroids undergo differentiation, as indicated by the appearance of functions of mature hepatocytes such as the detoxification of ammonia, albumin secretion, expression of the adult cytochrome P450 isozyme CYP3A4 and enzymatic activity typical of CYP2C9. Along with the expression of mature hepatic markers, these progenitor cells lost features typical of immature liver cells such as epithelial cell adhesion molecule. In addition to the acquisition of mature biochemical functions, the spheroids also developed a bile ducts, suggesting that they had differentiated into tissues resembling those in an intact liver.