TY - JOUR
T1 - Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure
AU - Chen, Yong
AU - Kobayashi, Naoya
AU - Suzuki, Satoshi
AU - Soto-Gutierrez, Alejandro
AU - Rivas-Carrillo, Jorge David
AU - Tanaka, Kimiaki
AU - Navarro-Alvarez, Nalú
AU - Fukazawa, Takuya
AU - Narushima, Michiki
AU - Miki, Atsushi
AU - Okitsu, Teru
AU - Amemiya, Hiroshi
AU - Tanaka, Noriaki
PY - 2005/5/27
Y1 - 2005/5/27
N2 - Background. Considering the scarcity of donor livers, it is extremely important to establish a functional culture method for isolated hepatocytes. As a tool for maintaining hepatocyte functions in vitro, dHGF, a variant of HGF (hepatocyte growth factor) with a deletion of five amino acids, attracted our attention because it is less cytotoxic compared with HGF. Methods. We evaluated growth, albumin production, metabolizing abilities of ammonia, lidocaine, and diazepam of human hepatocytes in the presence of dHGF (10-1000 ng/ml). The gene expression of liver markers was comparatively analyzed. The effect of intrasplenic transplantation of dHGF-treated human hepatocytes into severe combined immunodeficient (SCID) mice was evaluated in an acute liver failure (ALF) model induced by D-galactosamine (D-gal). Results. When 100 ng/ml of dHGF was utilized, metabolism rates of ammonia, lidocaine, and diazepam and albumin production per unit cell significantly increased. The gene expression analysis demonstrated the enhanced expression of albumin, HNF-4α, and C/EBPα in the hepatocytes treated with 100 ng/ml of dHGF. Transplantation of such hepatocytes prolonged the survival of the SCID mice with ALF induced by D-gal. Conclusions. The present work clearly demonstrates the usefulness of dHGF (100 ng/ml) for maintaining the differentiated functions of human hepatocytes in tissue culture.
AB - Background. Considering the scarcity of donor livers, it is extremely important to establish a functional culture method for isolated hepatocytes. As a tool for maintaining hepatocyte functions in vitro, dHGF, a variant of HGF (hepatocyte growth factor) with a deletion of five amino acids, attracted our attention because it is less cytotoxic compared with HGF. Methods. We evaluated growth, albumin production, metabolizing abilities of ammonia, lidocaine, and diazepam of human hepatocytes in the presence of dHGF (10-1000 ng/ml). The gene expression of liver markers was comparatively analyzed. The effect of intrasplenic transplantation of dHGF-treated human hepatocytes into severe combined immunodeficient (SCID) mice was evaluated in an acute liver failure (ALF) model induced by D-galactosamine (D-gal). Results. When 100 ng/ml of dHGF was utilized, metabolism rates of ammonia, lidocaine, and diazepam and albumin production per unit cell significantly increased. The gene expression analysis demonstrated the enhanced expression of albumin, HNF-4α, and C/EBPα in the hepatocytes treated with 100 ng/ml of dHGF. Transplantation of such hepatocytes prolonged the survival of the SCID mice with ALF induced by D-gal. Conclusions. The present work clearly demonstrates the usefulness of dHGF (100 ng/ml) for maintaining the differentiated functions of human hepatocytes in tissue culture.
KW - Acute liver failure
KW - Hepatocyte
KW - Hepatocyte growth factor
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UR - http://www.scopus.com/inward/citedby.url?scp=21144455177&partnerID=8YFLogxK
U2 - 10.1097/01.TP.0000160813.37515.97
DO - 10.1097/01.TP.0000160813.37515.97
M3 - Article
C2 - 15912107
AN - SCOPUS:21144455177
SN - 0041-1337
VL - 79
SP - 1378
EP - 1385
JO - Transplantation
JF - Transplantation
IS - 10
ER -