Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration.
Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration.
复制标题
参与肝和胆道再生的茎/祖细胞生态位。
DOI：
10.1155/2016/3658013
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发表时间：
2016
影响因子：
4.3
通讯作者：
Gaudio E
中科院分区：
文献类型：
--
作者：
Carpino G;Renzi A;Franchitto A;Cardinale V;Onori P;Reid L;Alvaro D;Gaudio E
含有干细胞/祖细胞的小生境存在于沿着人胆管树和肝腺泡内的不同解剖位置。最原始的干/祖细胞，胆管树干/祖细胞（BTSC），驻留在位于整个大的肝外和肝内胆管的胆管周围腺体内。BTSC是多能的，并且可以向肝和胰腺细胞命运分化。这些小生境的基质化学和其他特征是不确定的。Hering管（胆管）位于门静脉周围，含有肝干细胞/祖细胞（HpSC），参与肝内小胆管的更新，是肝细胞和胆管细胞的前体。小生境还含有肝星状细胞和内皮细胞、巨噬细胞的前体，并具有富含透明质酸、最低硫酸化蛋白聚糖、胎儿胶原和层粘连蛋白的基质化学。微环境提供驱动HpSC活化和分化的关键信号。新发现的第三个小生境是肝腺泡内的中央周围，含有Axin 2+单能肝细胞祖细胞，其侧缘与形成中央静脉的内皮细胞相连，并有助于成熟肝细胞的正常周转。它们与其他干/祖细胞的关系尚未确定。干细胞/祖细胞生态位在肝脏和胆道树的再生医学以及导致这些组织疾病的致病过程中具有重要意义。
Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches' matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin2+ unipotent hepatocytic progenitors linked on their lateral borders to endothelia forming the central vein, and contribute to normal turnover of mature hepatocytes. Their relationship to the other stem/progenitors is undefined. Stem/progenitor niches have important implications in regenerative medicine for the liver and biliary tree and in pathogenic processes leading to diseases of these tissues.