Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model.
BACKGROUND
The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage. We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction.


METHODS
We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Subsequently, we induced selective liver injury to recipient mice by DT administration. We then evaluated the engraftment of the transplanted cells and their effect on survivorship.


RESULTS
The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice. The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes. They continued to proliferate, forming clusters. The survival rate at 25 days after transplantation of the cell-transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%).


CONCLUSIONS
The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation.
Machimoto
Takafumi
T
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yasuchika
Kentaro
K
Komori
Junji
J
Ishii
Takamichi
T
Kamo
Naoko
N
Shimoda
Masayuki
M
Konishi
Sayuri
S
Saito
Michiko
M
Kohno
Kenji
K
Uemoto
Shinji
S
Ikai
Iwao
I
D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004167:Diphtheria Toxin / Q000633:toxicity; D004195:Disease Models, Animal; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D017093:Liver Failure / Q000139:chemically induced / Q000401:mortality / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins