Embryonic stem cells: hepatic differentiation and regenerative medicine for the treatment of liver disease.
Embryonic stem cells: hepatic differentiation and regenerative medicine for the treatment of liver disease.
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DOI：
10.2174/157488806776956878
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Teraoka, Hirobumi
中科院分区：
文献类型：
--
作者：
Asahina, Kinji;Teramoto, Kenichi;Teraoka, Hirobumi
肝细胞移植被认为是一种潜在的肝病治疗方法，也是等待肝移植患者的桥梁，但其应用受到肝细胞供应有限的阻碍。从小鼠和人类早期胚胎建立的胚胎干细胞（ES）是多能的，在体外以未分化状态无限增殖。由于ES细胞的分化似乎重演了早期胚胎发育，如果肝细胞可以在体外有效地产生，ES细胞可能成为细胞替代疗法的可移植肝细胞的来源。胚胎干细胞在体外可分化为肝细胞，并发现胚胎干细胞分化的肝细胞可表达许多肝细胞相关基因，并具有肝脏功能。然而，目前尚不清楚从ES细胞分化的肝细胞是来自定形内胚层还是原始内胚层。由于内脏内胚层来源于原始内胚层，表达许多肝细胞相关基因，并且注定形成胚外卵黄囊组织，而不是形成肝细胞，因此ES细胞必须在体外定向为定形内胚层谱系。本文讨论了胚胎干细胞在体外向肝细胞的分化与早期胚胎发生的比较，并描述了胚胎干细胞来源的肝细胞移植的疗效。
Hepatocyte transplantation is considered a potential treatment for liver diseases and a bridge for patients awaiting liver transplantation, but its application has been hampered by a limited supply of hepatocytes. Embryonic stem (ES) cells established from early mouse and human embryos are pluripotent, and proliferate indefinitely in an undifferentiated state in vitro. Since differentiation from ES cells seems to recapitulate early embryonic development, if hepatocytes could be efficiently generated in vitro, ES cells might become a source of transplantable hepatocytes for cell replacement therapy. Hepatocytes have been generated from ES cells in vitro, and the hepatocytes differentiated from ES cells have been found to express many hepatocyte-related genes and perform hepatic functions. However, it remains unclear whether the hepatocytes differentiated from ES cells are derived from definitive endoderm or primitive endoderm. Because visceral endoderm, which expresses many hepatocyte-related genes, is derived from primitive endoderm and is fated to form extraembryonic yolk sac tissues, not to form hepatocytes, ES cells must be directed to a definitive endoderm lineage in vitro. This article discusses the differentiation of ES cells into hepatocytes in vitro in comparison with early embryogenesis, and describes the efficacy of ES cell-derived hepatocyte transplantation.