The hepatic stem cell niche: Identification by label-retaining cell assay

The hepatic stem cell niche: Identification by label-retaining cell assay
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DOI:
10.1002/hep.22218
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发表时间:
2008-06-01
期刊:
影响因子:
13.5
通讯作者:
Theise, Neil D.
Theise, Neil D.
中科院分区:
医学1区
文献类型:
--
作者:
Kuwahara, Reiichiro;Kofman, Alexander V.;Theise, Neil D.

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标记保留测定仍然是最先进的方法,以确定器官内上皮干细胞壁龛的位置,在原位和体内。它们通常用于具有快速细胞更新的器官,但尚未应用于细胞更新非常缓慢的肝脏。我们使用亚致死剂量的对乙酰氨基酚与溴脱氧尿苷同时给药,使小鼠体内可能的肝干细胞负载标记物,然后给予第二次亚致死剂量的对乙酰氨基酚,以完成标记物从转运扩增细胞群中的“洗脱”。结论:四个可能的肝干细胞壁龛确定这种方法:管的Hering(近端胆管树),小叶内胆管,管周的“空”单核细胞,和胆管周围肝细胞。这些结果证实了几种不同的,往往是相互矛盾的线的调查有关肝内的干/祖细胞的位置,并建议肝脏有一个多层次的,灵活的再生系统,而不是一个单一的干/祖细胞的位置。
Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations. Conclusion: Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location.