Stem and progenitor cell systems in liver development and regeneration
Stem and progenitor cell systems in liver development and regeneration
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DOI：
10.1111/hepr.12349
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发表时间：
2015-01
影响因子：
4.2
通讯作者：
A. Kamiya;Y. Inagaki
中科院分区：
文献类型：
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作者：
A. Kamiya;Y. Inagaki
肝脏包括两个干/祖细胞系统：胎儿和成人肝脏干/祖细胞。胎肝前体细胞来源于前肠内胚层，在肝脏发育过程中分化为成熟的肝细胞和胆管细胞。成人肝祖细胞有助于严重和慢性肝损伤后的再生。然而，这些体肝干/祖细胞的特性仍然未知。最近建立了可用于分析这些细胞的培养系统，并鉴定了肝干/祖细胞特异性表面标志物，包括δ样1同源物（DLK）、分化簇（CD）13、CD 133和LIV 2。使用针对这些标志物的抗体纯化的细胞在体外和体内增殖延长的时间并分化成成熟细胞。最近建立了迫使人胚胎干细胞和诱导多能干细胞（iPS）分化为肝祖细胞的方法。我们证明了人iPS衍生细胞的CD 13 + CD 133+部分含有大量肝祖细胞样细胞。这些来自体组织和多能干细胞的肝干/祖细胞的分析将有助于开发严重肝病的新疗法。
The liver comprises two stem/progenitor cell systems: fetal and adult liver stem/progenitor cells. Fetal hepatic progenitor cells, derived from foregut endoderm, differentiate into mature hepatocytes and cholangiocytes during liver development. Adult hepatic progenitor cells contribute to regeneration after severe and chronic liver injuries. However, the characteristics of these somatic hepatic stem/progenitor cells remain unknown. Culture systems that can be used to analyze these cells were recently established and hepatic stem/progenitor cell‐specific surface markers including delta‐like 1 homolog (DLK), cluster of differentiation (CD) 13, CD133, and LIV2 were identified. Cells purified using antibodies against these markers proliferate for an extended period and differentiate into mature cells both in vitro and in vivo. Methods to force the differentiation of human embryonic stem and induced pluripotent stem (iPS) cells into hepatic progenitor cells have been recently established. We demonstrated that the CD13+CD133+ fraction of human iPS‐derived cells contained numerous hepatic progenitor‐like cells. These analyses of hepatic stem/progenitor cells derived from somatic tissues and pluripotent stem cells will contribute to the development of new therapies for severe liver diseases.