TY - JOUR
T1 - Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure
AU - Kobayashi, Naoya
AU - Miyazaki, Masahiro
AU - Fukaya, Kenichi
AU - Inoue, Yusuke
AU - Sakaguchi, Masakiyo
AU - Uemura, Tadahiro
AU - Noguchi, Hirofumi
AU - Kondo, Asami
AU - Tanaka, Noriaki
AU - Namba, Masayoshi
PY - 2000/1/27
Y1 - 2000/1/27
N2 - 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.
AB - 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.
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U2 - 10.1097/00007890-200001270-00002
DO - 10.1097/00007890-200001270-00002
M3 - Article
C2 - 10670627
AN - SCOPUS:0034719370
VL - 69
SP - 202
EP - 207
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 2
ER -