TY - JOUR
T1 - Expansion of human hepatocyte populations by a retroviral gene transfer of simian virus 40 large T antigen
AU - Kobayashi, Naoya
AU - Westerman, Karen A.
AU - Taguchi, Takehito
AU - Sakaguchi, Masakiyo
AU - Fujiwara, Toshiyoshi
AU - Urata, Haruo
AU - Kishimoto, Noboru
AU - Hayashi, Nobuyuki
AU - Nakaji, Shuhei
AU - Murakami, Takuro
AU - Leboulch, Philippe
AU - Tanaka, Noriaki
PY - 2001
Y1 - 2001
N2 - A hybrid artificial liver (HAL) could be used to treat acute liver failure or to serve as a temporary support until orthotopic liver transplantation is available. Primary human hepatocytes are ideal as a source of hepatic function in a HAL device. However, the worldwide shortage of human livers available for hepatocyte isolation severely limits this form of therapy. A possible alternative is to use a tightly regulated cell line that can be economically grown in culture to have differentiated liver function. In this work, human hepatocytes were immortalized with a retroviral vector SSR#69 expressing the genes of simian virus 40 large T antigen and herpes simplex virus-thymidine kinase. One of the resulting clones, NKNT-3, showed the gene expression of differentiated liver function and were sensitive to the antiviral agent ganciclovir. When transplanted into the spleen Of rats subjected to 90% hepatectomy, NKNT-3 cells prolonged the survival of 90% hepatectomized rats. The cells provide the advantages of unlimited availability, sterility, uniformity, and freedom from pathogens. This work represents a potential novel strategy for resolving the organ shortage that currently limits the use of primary human hepatocytes to develop a HAL.
AB - A hybrid artificial liver (HAL) could be used to treat acute liver failure or to serve as a temporary support until orthotopic liver transplantation is available. Primary human hepatocytes are ideal as a source of hepatic function in a HAL device. However, the worldwide shortage of human livers available for hepatocyte isolation severely limits this form of therapy. A possible alternative is to use a tightly regulated cell line that can be economically grown in culture to have differentiated liver function. In this work, human hepatocytes were immortalized with a retroviral vector SSR#69 expressing the genes of simian virus 40 large T antigen and herpes simplex virus-thymidine kinase. One of the resulting clones, NKNT-3, showed the gene expression of differentiated liver function and were sensitive to the antiviral agent ganciclovir. When transplanted into the spleen Of rats subjected to 90% hepatectomy, NKNT-3 cells prolonged the survival of 90% hepatectomized rats. The cells provide the advantages of unlimited availability, sterility, uniformity, and freedom from pathogens. This work represents a potential novel strategy for resolving the organ shortage that currently limits the use of primary human hepatocytes to develop a HAL.
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U2 - 10.1097/00002480-200109000-00017
DO - 10.1097/00002480-200109000-00017
M3 - Article
C2 - 11575822
AN - SCOPUS:0034821563
VL - 47
SP - 481
EP - 485
JO - ASAIO Journal
JF - ASAIO Journal
SN - 1058-2916
IS - 5
ER -