PMID- 12821039
OWN - NLM
STAT- MEDLINE
DCOM- 20040311
LR  - 20190817
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 39
IP  - 1
DP  - 2003 Jul
TI  - Sera from liver failure patients and a demethylating agent stimulate 
      transdifferentiation of murine bone marrow cells into hepatocytes in coculture 
      with nonparenchymal liver cells.
PG  - 17-23
AB  - BACKGROUND/AIMS: The plasticity of bone marrow cells (BMCs) is shown by their 
      ability to differentiate into mesenchymal as well as endodermal and ectodermal 
      lineages. Transdifferentiation of BMCs into hepatocytes has also been 
      demonstrated, both in vitro and in vivo. In the present study we investigated the 
      effects of liver nonparenchymal cells (NPCs) and sera from liver failure patients 
      (HSLF) on the in vitro transdifferentiation of murine BMCs into hepatocytes. 
      METHODS: Liver NPCs from wild-type mice, and 5-azacytidine-treated BMCs from 
      green fluorescence protein transgenic mice, were cocultured in medium containing 
      HSLF in combination with several cytokines. Hepatocyte-specific gene expression 
      in BMCs was identified by immunocytochemistry and reverse 
      transcription-polymerase chain reaction. RESULTS: Bone marrow cell-derived 
      hepatocyte-like colonies appeared after several days of coculture in medium 
      containing HSLF, oncostatin M (OSM) and hepatocyte growth factor (HGF). These 
      colonies expressed hepatocyte-specific genes. Transdifferentiation was enhanced 
      by 5-azacytidine treatment, and by HSLF, OSM and HGF. It did not take place when 
      the BMCs were separated from the NPCs in a dual chamber dish, or cultured with 
      other mesenchymal cells. CONCLUSIONS: Direct interaction of murine BMCs with 
      liver NPCs, as well as soluble factors in the HSLF and a demethylating agent, 
      strongly stimulate transdifferentiation into hepatocytes.
FAU - Yamazaki, Shintaro
AU  - Yamazaki S
AD  - Third Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
FAU - Miki, Kenji
AU  - Miki K
FAU - Hasegawa, Kiyoshi
AU  - Hasegawa K
FAU - Sata, Masataka
AU  - Sata M
FAU - Takayama, Tadatoshi
AU  - Takayama T
FAU - Makuuchi, Masatoshi
AU  - Makuuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Blood Proteins)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Azacitidine/*pharmacology
MH  - Blood Proteins/pharmacology
MH  - Bone Marrow Cells/*cytology/drug effects
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation/drug effects
MH  - Child
MH  - Coculture Techniques
MH  - Hepatocytes/*cytology/drug effects
MH  - Humans
MH  - Liver/cytology
MH  - Liver Failure/*blood
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Middle Aged
EDAT- 2003/06/25 05:00
MHDA- 2004/03/12 05:00
CRDT- 2003/06/25 05:00
PHST- 2003/06/25 05:00 [pubmed]
PHST- 2004/03/12 05:00 [medline]
PHST- 2003/06/25 05:00 [entrez]
AID - S0168827803001508 [pii]
AID - 10.1016/s0168-8278(03)00150-8 [doi]
PST - ppublish
SO  - J Hepatol. 2003 Jul;39(1):17-23. doi: 10.1016/s0168-8278(03)00150-8.