Hepatocyte transplantation in rats with decompensated cirrhosis

Naoya Kobayashi, Masahiro Ito, Junta Nakamura, Jin Cai, Chen Gao, James M Hammel, Ira J. Fox

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL4) and animals were studied only when evidence of liver failure did not improve when eel4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P < .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P < .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P < .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

Original languageEnglish (US)
Pages (from-to)851-857
Number of pages7
JournalHepatology
Volume31
Issue number4
DOIs
StatePublished - Jan 1 2000

Fingerprint

Hepatocytes
Fibrosis
Transplantation
Isogeneic Transplantation
Eagles
Survival
Hepatic Encephalopathy
Acute Liver Failure
Carbon Tetrachloride
Liver
Prothrombin Time
Liver Failure
Laboratory Animals
Phenobarbital
Bilirubin
Ammonia
Serum Albumin
Bone Marrow Cells
Liver Cirrhosis
Body Weight

ASJC Scopus subject areas

  • Hepatology

Cite this

Kobayashi, N., Ito, M., Nakamura, J., Cai, J., Gao, C., Hammel, J. M., & Fox, I. J. (2000). Hepatocyte transplantation in rats with decompensated cirrhosis. Hepatology, 31(4), 851-857. https://doi.org/10.1053/he.2000.5636

Hepatocyte transplantation in rats with decompensated cirrhosis. / Kobayashi, Naoya; Ito, Masahiro; Nakamura, Junta; Cai, Jin; Gao, Chen; Hammel, James M; Fox, Ira J.

In: Hepatology, Vol. 31, No. 4, 01.01.2000, p. 851-857.

Research output: Contribution to journalArticle

Kobayashi, N, Ito, M, Nakamura, J, Cai, J, Gao, C, Hammel, JM & Fox, IJ 2000, 'Hepatocyte transplantation in rats with decompensated cirrhosis', Hepatology, vol. 31, no. 4, pp. 851-857. https://doi.org/10.1053/he.2000.5636
Kobayashi N, Ito M, Nakamura J, Cai J, Gao C, Hammel JM et al. Hepatocyte transplantation in rats with decompensated cirrhosis. Hepatology. 2000 Jan 1;31(4):851-857. https://doi.org/10.1053/he.2000.5636
Kobayashi, Naoya ; Ito, Masahiro ; Nakamura, Junta ; Cai, Jin ; Gao, Chen ; Hammel, James M ; Fox, Ira J. / Hepatocyte transplantation in rats with decompensated cirrhosis. In: Hepatology. 2000 ; Vol. 31, No. 4. pp. 851-857.
@article{9b1d5c3763c348b8a67b73ab21cf9b88,
title = "Hepatocyte transplantation in rats with decompensated cirrhosis",
abstract = "Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL4) and animals were studied only when evidence of liver failure did not improve when eel4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P < .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P < .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P < .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.",
author = "Naoya Kobayashi and Masahiro Ito and Junta Nakamura and Jin Cai and Chen Gao and Hammel, {James M} and Fox, {Ira J.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1053/he.2000.5636",
language = "English (US)",
volume = "31",
pages = "851--857",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Hepatocyte transplantation in rats with decompensated cirrhosis

AU - Kobayashi, Naoya

AU - Ito, Masahiro

AU - Nakamura, Junta

AU - Cai, Jin

AU - Gao, Chen

AU - Hammel, James M

AU - Fox, Ira J.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL4) and animals were studied only when evidence of liver failure did not improve when eel4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P < .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P < .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P < .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

AB - Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL4) and animals were studied only when evidence of liver failure did not improve when eel4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P < .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P < .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P < .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

UR - http://www.scopus.com/inward/record.url?scp=0034067582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034067582&partnerID=8YFLogxK

U2 - 10.1053/he.2000.5636

DO - 10.1053/he.2000.5636

M3 - Article

C2 - 10733539

AN - SCOPUS:0034067582

VL - 31

SP - 851

EP - 857

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -