Morphogenesis of primary human biliary epithelial cells: Induction in high-density culture or by coculture with autologous human hepatocytes
Morphogenesis of primary human biliary epithelial cells: Induction in high-density culture or by coculture with autologous human hepatocytes
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DOI：
10.1053/jhep.2001.22703
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发表时间：
2001-03-01
期刊：
影响因子：
13.5
通讯作者：
Strain, AJ
中科院分区：
文献类型：
--
作者：
Auth, MKH;Joplin, RE;Strain, AJ
虽然胆管形态发生的控制已经得到了一些关注，特别是使用分离的大鼠胆管上皮细胞模型，人胆管形成的调节还没有很好的定义。在本研究中，使用三维培养模型，包括原代人胆管上皮细胞（BECs）和原代人肝细胞共培养，我们试图定义所涉及的因素。我们已经表明，原代人BEC可以在胶原凝胶上扩增，在生长因子或血清的情况下。当在双胶原凝胶中以高密度铺板时，BEC建立了三维结构，随后发育成分化良好的极化管腔导管。这种形态发生反应发生在没有肝细胞生长因子（HGF）和表皮生长因子。引人注目的是，添加生长因子（在血清存在下）导致极性丧失，尽管细胞保留了对这两种因子的生长反应。BEC与自体肝细胞共培养增强了低密度BEC进行导管生成的能力。通过添加来自先前肝细胞-BEC共培养物的条件培养基来模拟这种效应。这些发现表明，对于人胆管形态发生，需要上皮细胞-细胞相互作用，但间充质来源的因子如HGF可能并不重要。
Although the control of biliary ductular morphogenesis has received some attention particularly using isolated rat biliary epithelial cell models, the regulation of human bile duct formation is not well defined. In the present study, using a 3-dimensional culture model comprising primary human biliary epithelial cells (BECs) and coculture with primary human hepatocytes, we have sought to define the factors involved. We have shown that primary human BECs can be expanded on collagen gels in the absence of growth factors or serum. When plated in high density in double collagen gels, BECs established 3-dimensional structures that subsequently developed into well differentiated polarized luminal ducts. This morphogenic response occurred in the absence of hepatocyte growth factor (HGF) and epidermal growth factor. Strikingly, the addition of growth factors (in the presence of serum) resulted in loss of polarity although the cells retained growth responses to both factors. Coculture of BECs with autologous human hepatocytes enhanced the ability of low-density BECs to undergo ductulo-genesis. This effect was mimicked by addition of conditioned medium from previous hepatocyte-BEC cocultures, These findings indicate that for human biliary ductular morphogenesis, epithelial cell-cell interactions are required but that mesenchymally derived factors such as HGF may not be important.