Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes.
Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.
Kobayashi
N
N
First Department of Surgery and Department of Cell Biology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Fujiwara
T
T
Westerman
K A
KA
Inoue
Y
Y
Sakaguchi
M
M
Noguchi
H
H
Miyazaki
M
M
Cai
J
J
Tanaka
N
N
Fox
I J
IJ
Leboulch
P
P
D000328:Adult; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D017690:Cell Transplantation; D015870:Gene Expression; D005822:Genetic Vectors; D006498:Hepatectomy; D006801:Humans; D019426:Integrases / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D008115:Liver Regeneration; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014162:Transfection; D014764:Viral Proteins
D000952:Antigens, Polyomavirus Transforming; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases