Hepatic differentiation of embryonic stem cells by murine fetal liver mesenchymal cells.
Hepatic differentiation of embryonic stem cells by murine fetal liver mesenchymal cells.
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DOI：
10.1007/978-1-62703-128-8_29
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发表时间：
2013
影响因子：
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通讯作者：
T. Ishii;K. Yasuchika;I. Ikai
中科院分区：
文献类型：
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作者：
T. Ishii;K. Yasuchika;I. Ikai
胚胎干细胞(ESCs)来源的肝细胞是再生医学的潜在细胞来源。然而，由于调控肝细胞分化的决定性生长因子和分子机制尚未很好地确定，因此将ESCs分化为成熟肝细胞在技术上一直是困难的。小鼠胎肝中存在CD45gp38+−CD49f+/−-Thy1+gp38+间充质细胞，通过细胞-细胞直接接触诱导肝祖细胞分化为成熟肝细胞。利用这些细胞，我们对胚胎干细胞的肝脏成熟采用了两步法：第一步，将胚胎干细胞分化为内皮细胞或肝祖细胞；第二，通过与小鼠胎肝间充质细胞共培养，将胚胎干细胞来源的内皮细胞成熟为有功能的肝细胞。ESC来源的肝细胞样细胞具有肝脏功能，包括氨去除活性、白蛋白分泌能力、糖原合成和储存以及细胞色素P450酶活性。
Hepatocytes derived from embryonic stem cells (ESCs) are a potential cell source for regenerative medicine. However, it has been technically difficult to differentiate ESCs into mature hepatocytes because the definitive growth factors and molecular mechanisms governing hepatocyte differentiation have not yet been well defined. The CD45−CD49f+/−Thy1+gp38+mesenchymal cells that reside in murine fetal livers induce hepatic progenitor cells to differentiate into mature hepatocytes by direct cell–cell contact. Utilizing these cells, we employ a two-step procedure for hepatic maturation of ESCs: first, ESCs are differentiated into endodermal cells or hepatic progenitor cells, and second, ESC-derived endodermal cells are matured into functional hepatocytes by coculture with murine fetal liver mesenchymal cells. The ESC-derived hepatocyte-like cells possess hepatic functions, including ammonia removal activity, albumin secretion ability, glycogen synthesis and storage, and cytochrome P450 enzymatic activity.