Efficacy and limitation of bone marrow transplantation in the treatment of acute and subacute liver failure in rats.
OBJECTIVE
Recent reports have shown that bone marrow cells (BMC) retain the potential to differentiate into hepatocytes. Thus, the BMC have been recognized as an attractive source for liver regenerative medicine. However, it has not been clarified whether BMC transplantation can be used to treat liver damage in vivo. In the present study, we explored whether BMC possess therapeutic potential to treat acute and/or subacute liver failure.


METHODS
Fulminant hepatic failure (FHF) was induced by 70% hepatectomy with ligation of the right lobe pedicle (24% liver mass), followed by transplantation of BMC into the spleen. Dipeptidyl peptidase IV-positive (DPPIV(+)) BMC were then transplanted into DPPIV-negative (DPPIV(-)) recipients following hepatic irradiation (HIR) in which 70% of the liver was resected and the remnant liver irradiated.


RESULTS
There was no benefit of BMC transplantation towards survival in the FHF model. DPPIV(+) hepatocytes appeared in the liver tissues of the DPPIV(-) HIR model rats, but DPPIV(+) hepatocytes replaced less than 13% of the recipient liver.


CONCLUSIONS
BMC transplantation may have limitations in the treatment of fulminant or acute liver failure because they do not have sufficient time to develop into functional hepatocytes. Preparative HIR may be beneficial in help to convert the transplanted BMC into host hepatocytes, and provide a survival benefit. Although, However, the precise mechanism warrants further studies.
Tokai
Hirotaka
H
Department of Surgery, Graduate School of Biochemical Sciences, Nagasaki University, Nagasaki, Japan.
Kawashita
Yujo
Y
Ito
Yuichiro
Y
Yamanouchi
Kosho
K
Takatsuki
Mitsuhisa
M
Eguchi
Susumu
S
Tajima
Yoshitsugu
Y
Kanematsu
Takashi
T