Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver.
BACKGROUND
Bone marrow cells (BMCs) have been shown to differentiate into a liver cell lineage, but little is known about their dynamics following transplantation. BMCs were cultured to investigate the expression of liver-specific genes in vitro and transplanted into in vivo liver-injury models to elucidate their dynamics in the liver.


METHODS
The mRNA expression of various liver-specific genes in BMCs cocultured with hepatocytes was analyzed using reverse transcription-polymerase chain reaction. BMCs from transgenic rats expressing green fiuorescent protein were transplanted into the spleen of rat liver-injury models induced with 2-acetylaminofiuorene (2-AAF) or carbon tetrachloride (CCl4). BMCs were also transplanted directly into livers treated with CCl4 to determine which route is better for transplantation.


RESULTS
BMCs differentiated into a liver cell lineage in vitro and expressed mRNAs consistent with mature hepatocytes, including albumin. The transplanted BMCs were found in the liver in the CCl4-induced injury model, but not in the 2-AAF-induced model. The hepatocyte growth factor and fibroblast growth factor mRNA levels in the liver were significantly higher in the CCl4-induced model than in the 2-AAF-induced model. Migration of BMCs to the liver was more effective following injection into the liver, rather than into the spleen.


CONCLUSIONS
Cultured BMCs differentiated into a liver cell lineage are a potential source for cell transplantation. Transplantation is successful in the severely injured liver with a high level of expression of mRNAs for growth factors. Injection of BMCs directly into the liver is the preferred route of administration.
Okumoto
Kazuo
K
Department of Gastroenterology, Course of Internal Medicine and Therapeutics, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
Saito
Takafumi
T
Haga
Hiroaki
H
Hattori
Etsuko
E
Ishii
Rika
R
Karasawa
Tetsuru
T
Suzuki
Akihiko
A
Misawa
Keiko
K
Sanjo
Mai
M
Ito
Jun-itsu
JI
Sugahara
Kazuhiko
K
Saito
Koji
K
Togashi
Hitoshi
H
Kawata
Sumio
S
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002454:Cell Differentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology*; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000473:pathology* / Q000601:surgery; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000601:surgery
D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D015073:2-Acetylaminofluorene; D002251:Carbon Tetrachloride