Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure

Yong Chen, Naoya Kobayashi, Satoshi Suzuki, Alejandro Soto-Gutierrez, Jorge David Rivas-Carrillo, Kimiaki Tanaka, Nalú Navarro-Alvarez, Takuya Fukazawa, Michiki Narushima, Atsushi Miki, Teru Okitsu, Hiroshi Amemiya, Noriaki Tanaka

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1378-1385
Number of pages8
JournalTransplantation
Volume79
Issue number10
DOIs
StatePublished - May 27 2005
Externally publishedYes

Fingerprint

Hepatocyte Growth Factor
Acute Liver Failure
Hepatocytes
Transplantation
Albumins
Galactosamine
SCID Mice
Diazepam
Lidocaine
Ammonia
Gene Expression
Liver
Amino Acids
Growth

Keywords

  • Acute liver failure
  • Hepatocyte
  • Hepatocyte growth factor

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure. / Chen, Yong; Kobayashi, Naoya; Suzuki, Satoshi; Soto-Gutierrez, Alejandro; Rivas-Carrillo, Jorge David; Tanaka, Kimiaki; Navarro-Alvarez, Nalú; Fukazawa, Takuya; Narushima, Michiki; Miki, Atsushi; Okitsu, Teru; Amemiya, Hiroshi; Tanaka, Noriaki.

In: Transplantation, Vol. 79, No. 10, 27.05.2005, p. 1378-1385.

Research output: Contribution to journalArticle

Chen, Y, Kobayashi, N, Suzuki, S, Soto-Gutierrez, A, Rivas-Carrillo, JD, Tanaka, K, Navarro-Alvarez, N, Fukazawa, T, Narushima, M, Miki, A, Okitsu, T, Amemiya, H & Tanaka, N 2005, 'Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure', Transplantation, vol. 79, no. 10, pp. 1378-1385. https://doi.org/10.1097/01.TP.0000160813.37515.97
Chen, Yong ; Kobayashi, Naoya ; Suzuki, Satoshi ; Soto-Gutierrez, Alejandro ; Rivas-Carrillo, Jorge David ; Tanaka, Kimiaki ; Navarro-Alvarez, Nalú ; Fukazawa, Takuya ; Narushima, Michiki ; Miki, Atsushi ; Okitsu, Teru ; Amemiya, Hiroshi ; Tanaka, Noriaki. / Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure. In: Transplantation. 2005 ; Vol. 79, No. 10. pp. 1378-1385.
@article{45ce4339dab94f26b8fa2cbffd5a1ca2,
title = "Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure",
abstract = "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.",
keywords = "Acute liver failure, Hepatocyte, Hepatocyte growth factor",
author = "Yong Chen and Naoya Kobayashi and Satoshi Suzuki and Alejandro Soto-Gutierrez and Rivas-Carrillo, {Jorge David} and Kimiaki Tanaka and Nal{\'u} Navarro-Alvarez and Takuya Fukazawa and Michiki Narushima and Atsushi Miki and Teru Okitsu and Hiroshi Amemiya and Noriaki Tanaka",
year = "2005",
month = "5",
day = "27",
doi = "10.1097/01.TP.0000160813.37515.97",
language = "English (US)",
volume = "79",
pages = "1378--1385",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

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

UR - http://www.scopus.com/inward/record.url?scp=21144455177&partnerID=8YFLogxK

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

VL - 79

SP - 1378

EP - 1385

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 10

ER -