PMID- 16629650
OWN - NLM
STAT- MEDLINE
DCOM- 20060915
LR  - 20191210
IS  - 1478-3223 (Print)
IS  - 1478-3223 (Linking)
VI  - 26
IP  - 4
DP  - 2006 May
TI  - Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation 
      during experimental cholestatic ductal hyperplasia.
PG  - 457-66
AB  - 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%alpha-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.
FAU - Moritoki, Yuki
AU  - Moritoki Y
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine, 
      Sendai Miyagi, Japan.
FAU - Ueno, Yoshiyuki
AU  - Ueno Y
FAU - Kanno, Noriatsu
AU  - Kanno N
FAU - Yamagiwa, Yoko
AU  - Yamagiwa Y
FAU - Fukushima, Koji
AU  - Fukushima K
FAU - Gershwin, M Eric
AU  - Gershwin ME
FAU - Shimosegawa, Tooru
AU  - Shimosegawa T
LA  - eng
GR  - DK39588/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Hes1 protein, mouse)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (KRT7 protein, human)
RN  - 0 (Keratin-7)
RN  - 0 (Krt7 protein, mouse)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (Transcription Factor HES-1)
RN  - 0 (Twf1 protein, mouse)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 551-06-4 (1-Naphthylisothiocyanate)
RN  - 68238-35-7 (Keratins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - 1-Naphthylisothiocyanate
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Bile Ducts/*cytology/pathology/*physiology
MH  - Bone Marrow Cells/*cytology/metabolism
MH  - Bone Marrow Transplantation
MH  - *Cell Differentiation
MH  - Cell Proliferation
MH  - Cholestasis/chemically induced/metabolism/*pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Hyperplasia/pathology
MH  - Keratin-7
MH  - Keratins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microfilament Proteins
MH  - Protein-Tyrosine Kinases/analysis/genetics/metabolism
MH  - Receptors, Notch/genetics/metabolism
MH  - *Regeneration
MH  - Transcription Factor HES-1
EDAT- 2006/04/25 09:00
MHDA- 2006/09/16 09:00
CRDT- 2006/04/25 09:00
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/09/16 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - LIV1250 [pii]
AID - 10.1111/j.1478-3231.2006.01250.x [doi]
PST - ppublish
SO  - Liver Int. 2006 May;26(4):457-66. doi: 10.1111/j.1478-3231.2006.01250.x.