Expansion of human hepatocyte populations by a retroviral gene transfer of simian virus 40 large T antigen

Naoya Kobayashi, Karen A. Westerman, Takehito Taguchi, Masakiyo Sakaguchi, Toshiyoshi Fujiwara, Haruo Urata, Noboru Kishimoto, Nobuyuki Hayashi, Shuhei Nakaji, Takuro Murakami, Philippe Leboulch, Noriaki Tanaka

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)481-485
Number of pages5
JournalASAIO Journal
Volume47
Issue number5
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

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    Kobayashi, N., Westerman, K. A., Taguchi, T., Sakaguchi, M., Fujiwara, T., Urata, H., Kishimoto, N., Hayashi, N., Nakaji, S., Murakami, T., Leboulch, P., & Tanaka, N. (2001). Expansion of human hepatocyte populations by a retroviral gene transfer of simian virus 40 large T antigen. ASAIO Journal, 47(5), 481-485. https://doi.org/10.1097/00002480-200109000-00017