Tanimizu Naoki, Mitaka Toshihiro
Department of Tissue Development and Regeneration; Research Institute for Frontier Medicine; Sapporo Medical University School of Medicine; Sapporo, Japan.
Organogenesis. 2014 Apr-Jun;10(2):208-15. doi: 10.4161/org.27591. Epub 2014 Jan 22.
Liver stem/progenitor cells (LPCs) are defined as cells that supply two types of liver epithelial cells, hepatocytes and cholangiocytes, during development, cellular turnover, and regeneration. Hepatoblasts, which are fetal LPCs derived from endoderm stem cells, robustly proliferate and differentiate into hepatocytes and cholangiocytes during fetal life. Between mid-gestation and the neonatal period, some cholangiocytes function as LPCs. Although LPCs in adult livers can be enriched in cells positive for cholangiocyte markers, their tissue localization and functions in cellular turnover remain obscure. On the other hand, it is well known that liver regeneration under conditions suppressing hepatocyte proliferation is supported by LPCs, though their origin has not been clearly identified. Recently many groups took advantage of new techniques including prospective isolation of LPCs by fluorescence-activated cell sorting and genetic lineage tracing to facilitate our understanding of epithelial supply in normal and injured livers. Those works suggest that, in normal livers, the turnover of hepatocytes mostly depends on duplication of hepatocytes. It is also demonstrated that liver epithelial cells as well as LPCs have great plasticity and flexible differentiation capability to respond to various types of injuries by protecting or repairing liver tissues.
肝干细胞/祖细胞(LPCs)被定义为在发育、细胞更新和再生过程中能够产生两种肝上皮细胞,即肝细胞和胆管细胞的细胞。肝母细胞是源自内胚层干细胞的胎儿LPCs,在胎儿期能强烈增殖并分化为肝细胞和胆管细胞。在妊娠中期至新生儿期,一些胆管细胞发挥LPCs的功能。尽管成年肝脏中的LPCs可在胆管细胞标志物阳性的细胞中富集,但其组织定位及在细胞更新中的功能仍不清楚。另一方面,众所周知,在抑制肝细胞增殖的条件下,肝再生由LPCs支持,尽管其来源尚未明确确定。最近,许多研究小组利用了包括通过荧光激活细胞分选对LPCs进行前瞻性分离和遗传谱系追踪等新技术,以促进我们对正常和受损肝脏中上皮细胞供应的理解。这些研究表明,在正常肝脏中,肝细胞的更新主要依赖于肝细胞的复制。研究还表明,肝上皮细胞以及LPCs具有很大的可塑性和灵活的分化能力,通过保护或修复肝组织来应对各种类型的损伤。