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Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasia
Author(s) -
Moritoki Yuki,
Ueno Yoshiyuki,
Kanno Noriatsu,
Yamagiwa Yoko,
Fukushima Koji,
Gershwin M. Eric,
Shimosegawa Tooru
Publication year - 2006
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01250.x
Subject(s) - cholangiocyte , cholestasis , hes1 , cytokeratin , biology , stem cell , bone marrow , cancer research , proliferating cell nuclear antigen , hyperplasia , stromal cell , cell growth , pathology , hepatocyte growth factor , endocrinology , medicine , receptor , immunology , microbiology and biotechnology , immunohistochemistry , signal transduction , notch signaling pathway , genetics
Background: Ductopenia is observed in end‐stage human cholestatic diseases. The limited capability of cholangiocytes for proliferation is suggested to be the principal reason. Recently, bone marrow cells (BMCs) have been reported to behave as hepatic stem cells; however, their capability to differentiate into cholangiocytes in cholestasis remains unclear. Methods: Normal mice were lethally irradiated to suppress the proliferation of self‐BMCs; thereafter, the BMCs from enhanced green fluorescent protein (EGFP)‐transgenic mice were transferred to recipients. Chronic cholestasis was induced by 0.1%α‐naphtylisothiocyanate (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed morphologically and immunohistchemically (cytokeratin‐7 (CK‐7), A6). Proliferative activity (proliferating cell nuclear antigen (PCNA) protein expression), hepatic growth factor (HGF) receptor (c‐Met), stem cell factor receptor (c‐kit), Notch2 and Hes1 expression were also evaluated. Results: Marked cholangiocyte proliferation was observed in ANIT‐fed mice. However, no EGFP/CK‐7 double positive cells were identified in any of the liver specimens after BMCs transfer (Tx). In hepatic parenchyma, there were scattered EGFP‐positive cells, although none of them were positive for CK‐7. Conclusions: In spite of the significant ductular proliferations after ANIT feeding, no EGFP‐positive cholangiocytes were confirmed by any other means in this chronic cholestasis model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the differentiation of cholangiocytes. Future studies are feasible to clarify the origin of proliferative cholangiocytes observed in this chronic cholestatic ductular hyperplasia model.