Foetal hepatic progenitor cells assume a cholangiocytic cell phenotype during two-dimensional pre-culture.
Foetal hepatic progenitor cells assume a cholangiocytic cell phenotype during two-dimensional pre-culture.
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DOI：
10.1038/srep28283
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发表时间：
2016-06-23
影响因子：
4.6
通讯作者：
Kamiya A
中科院分区：
文献类型：
--
作者：
Anzai K;Chikada H;Tsuruya K;Ida K;Kagawa T;Inagaki Y;Mine T;Kamiya A
肝脏由实质肝细胞和其他细胞组成。肝祖细胞（LPC）是肝细胞和胆管细胞的来源。因此，对LPCs向这些功能细胞分化的调控机制的分析，对于利用祖细胞进行肝再生治疗具有重要意义。在3D培养中发现成人肝脏中的LPC形成具有胆管细胞特征的囊肿。相比之下，胎儿LPCs不能在同一培养物中形成这些胆管细胞囊肿。因此，胎儿LPCs向胆管祖细胞的转变可能发生在肝脏发育过程中。来源于鼠胎肝的原代CD45−Ter119−Dlk1+ LPC在3D培养中形成白蛋白（ALB）+细胞角蛋白（CK）19−非胆管细胞囊肿。相反，当胎儿LPC在明胶包被的培养皿上预培养时，它们形成ALB− CK 19+胆管细胞囊肿。当肝细胞生长因子或抑瘤素M，这是肝细胞分化的诱导剂，加入到预培养，LPCs没有形成胆管囊肿。这些结果表明，在明胶包被的培养皿上的预培养改变了胎儿LPCs的特征为胆管细胞。此外，新生肝祖细胞能够在3D培养中形成胆管细胞囊肿而无需预培养。因此，中期胎儿LPC的体外预培养有可能替代体内晚期胎儿成熟步骤。
Liver consists of parenchymal hepatocytes and other cells. Liver progenitor cell (LPC) is the origin of both hepatocytes and cholangiocytic cells. The analyses of mechanism regulating differentiation of LPCs into these functional cells are important for liver regenerative therapy using progenitor cells. LPCs in adult livers were found to form cysts with cholangiocytic characteristics in 3D culture. In contrast, foetal LPCs cannot form these cholangiocytic cysts in the same culture. Thus, the transition of foetal LPCs into cholangiocytic progenitor cells might occur during liver development. Primary CD45−Ter119−Dlk1+ LPCs derived from murine foetal livers formed ALBUMIN (ALB)+CYTOKERATIN (CK)19− non-cholangiocytic cysts within 3D culture. In contrast, when foetal LPCs were pre-cultured on gelatine-coated dishes, they formed ALB−CK19+ cholangiocytic cysts. When hepatocyte growth factor or oncostatin M, which are inducers of hepatocytic differentiation, was added to pre-culture, LPCs did not form cholangiocytic cysts. These results suggest that the pre-culture on gelatine-coated dishes changed the characteristics of foetal LPCs into cholangiocytic cells. Furthermore, neonatal liver progenitor cells were able to form cholangiocytic cysts in 3D culture without pre-culture. It is therefore possible that the pre-culture of mid-foetal LPCs in vitro functioned as a substitute for the late-foetal maturation step in vivo.