Transforming growth factor-alpha accelerates hepatocyte repopulation after hepatocyte transplantation.
OBJECTIVE
Although hepatocyte transplantation could be an alternative to orthotopic liver transplantation, many problems, such as rejection, location, required volume, and hepatocyte activity are currently unresolved. We previously demonstrated an anti-apoptotic effect in transgenic mice overexpressing transforming growth factor (TGF)-alpha. We herein present the details of a successful hepatocyte transplantation using TGF-alpha transgenic mice.


METHODS
We used transgenic (TG) mice which overexpressed human TGF-alpha controlled by the metallothionein promoter. Wild-type mice were used as the controls (WT). Parenchymal hepatocytes were isolated from an adult mouse by the modified in situ perfusion method. The proliferation and resistance to Fas-induced apoptosis were examined in vitro. In addition, we transplanted the parenchymal hepatocytes into the peritoneal cavity of the WT mice.


RESULTS
The TG hepatocytes showed higher proliferative activity and more resistance to Fas-induced apoptosis in comparison to the WT hepatocytes. Moreover, an immunohistochemical analysis demonstrated that the transplanted TG hepatocytes increased more in size and showed a higher expression of CD31 and vascular endothelial growth factor in comparison to the WT hepatocytes. We also observed that albumin was expressed in equal amounts in both types of transplanted hepatocytes.


CONCLUSIONS
Cell transplantation with TGF-alpha overexpressing hepatocytes could preserve hepatocyte function.
Kosone
Takashi
T
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
Takagi
Hitoshi
H
Horiguchi
Norio
N
Kakizaki
Satoru
S
Sato
Ken
K
Watanabe
Yoshifumi
Y
Mori
Masatomo
M
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D049109:Cell Proliferation; D048429:Cell Size; D004351:Drug Resistance; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
D000418:Albumins; D000906:Antibodies; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D019014:fas Receptor