Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells
Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells
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DOI：
10.1016/s0168-8278(03)00309-x
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发表时间：
2003-09-01
影响因子：
25.7
通讯作者：
Theise, ND
中科院分区：
文献类型：
--
作者：
Falkowski, O;An, HJ;Theise, ND
背景/目标：在大面积肝坏死中，肝干细胞构成了Hering衍生的管道，细胞角蛋白19（CK 19）阳性的“导管反应”（DR）。肝硬化中的DR是否是活化的干细胞（所谓的“芽”）或胆汁淤积的胆汁化生，损伤的肝细胞仍有争议。我们研究了来自DR和肝硬化胆汁树的间隔内肝细胞（ISHS）的来源。方法：检查了B型和C型肝炎、酒精性、原发性、胆汁性肝硬化和原发性硬化性胆管炎相关肝硬化的组织块。对ISH进行量化，并记录其与DR和胆汁淤积的相关性。结果：830例ISH中有775例（94%）伴CK 19阳性DR，无胆管反应的ISH更易出现胆汁淤积（P < 0.0001）。在3D中，可以看到ISH直接从胆管树出芽。总的来说：ISH：（1）通常与干细胞样DR相关;（2）很少是胆汁淤积性的，导致相关DR无法解释;（3）与3D胆道系统相关。丙型肝炎随着时间的推移动态增殖率表明，肝细胞复制减少在后期阶段，与相关的激活的胆道干细胞compartment.Conclusions：因此，我们认为，胆道树，至少从其较小的分支到运河的赫林，是由或至少港湾兼性肝干细胞，ISH主要代表'芽'的新形成的肝细胞。(C)2003年由Elsevier B. V.代表欧洲肝脏研究协会出版。
Background/Aims: In massive hepatic necrosis, hepatic stem cells constitute a canal of Hering derived, cytokeratin 19 (CK19) positive 'ductular reaction' (DR). Whether DRs in cirrhosis are activated stem cells (so called 'buds') or biliary metaplasia of cholestatic, injured hepatocytes is still debated. We investigate derivation of intraseptal hepatocytes (ISHs) from DRs and from the biliary tree in cirrhosis.Methods: Explants of hepatitis B and C, alcohol, primary, biliary cirrhosis and primary sclerosing cholangitis-related cirrhosis were examined. ISHs were quantified and their associations with DRs and cholestasis recorded. 3D-reconstruction of ISHs and nearby bile ducts was performed in blocks from hepatitis C and primary sclerosing cholangitis cirrhosis.Results: Seven hundred seventy five/830 (94%) ISHs were associated with CK19 positive DRs. ISHs without ductular reactions were more likely to show cholestatic features (P < 0.0001). In 3D, ISHs were seen to bud directly from the biliary tree. In summary: ISHs: (1) are usually associated with stem cell-like DRs; (2) are rarely cholestatic, leaving the associated DRs unexplained; and (3) are linked to the biliary tree in 3D. Dynamic proliferation rates in hepatitis C over time suggest that hepatocyte replication diminishes in late stages, with an associated activation of the biliary stem cell compartment.Conclusions: We therefore suggest that the biliary tree, from at least its smaller branches up to the canals of Hering, are composed of or at least harbor facultative hepatic stem cells, and that ISH largely represent 'buds' of newly formed hepatocytes. (C) 2003 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.