Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells

被引:157
作者
Falkowski, O
An, HJ
Ianus, IA
Chiriboga, L
Yee, H
West, AB
Theise, ND
机构
[1] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Digest Dis, New York, NY 10003 USA
[2] Yeshiva Univ, Dept Pathol, Albert Einstein Coll Med, Bronx, NY USA
[3] Pochon CHA Univ, Dept Pathol, Coll Med, Sungnam, South Korea
[4] NYU, Sch Med, Dept Pathol, New York, NY USA
关键词
progenitor cells; liver;
D O I
10.1016/S0168-8278(03)00309-X
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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收藏
页码:357 / 364
页数:8
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