Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure

Naoya Kobayashi, Masahiro Miyazaki, Kenichi Fukaya, Yusuke Inoue, Masakiyo Sakaguchi, Tadahiro Uemura, Hirofumi Noguchi, Asami Kondo, Noriaki Tanaka, Masayoshi Namba

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Abstract

Background. Temporary support of a damaged liver by a bioartificial liver (BAL) devise is a promising approach for the treatment of acute liver failure. Although human primary hepatocytes are an ideal source of hepatic function in BAL, shortage of human livers available for hepatocyte isolation is the limiting factor for the use of this modality. A clonal human hepatocyte cell line that can grow economically in culture and exhibit liver- specific functions should be an attractive solution to this problem. Methods. To test this alternative, primary human fetal hepatocytes were immortalized using Simian virus 40 large T antigen. To investigate the potential of the immortalized cells for BAL, we transplanted the cells into the spleen of adult rats and performed a 90% hepatectomy 12 hr later. Results. One of the cloned human liver cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplanting of 20 x 106 OUMS-29 cells protected the animals from hyperammonemia and the associated hepatic encephalopathy. Survival was significantly prolonged in 90% of hepatectomized rats receiving OUMS-29 cells. Conclusions. A highly differentiated immortalized human hepatocyte cell line, OUMS-29, was able to provide metabolic support during acute liver failure induced by 90% hepatectomy in rats. Essentially unlimited availability of OUMS-29 cells may be clinically useful for BAL treatment.

Original languageEnglish
Pages (from-to)202-207
Number of pages6
JournalTransplantation
Volume69
Issue number2
DOIs
Publication statusPublished - Jan 27 2000

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ASJC Scopus subject areas

  • Transplantation

Cite this

Kobayashi, N., Miyazaki, M., Fukaya, K., Inoue, Y., Sakaguchi, M., Uemura, T., Noguchi, H., Kondo, A., Tanaka, N., & Namba, M. (2000). Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure. Transplantation, 69(2), 202-207. https://doi.org/10.1097/00007890-200001270-00002