Transplantation of bone marrow cells decreases tumor necrosis factor-α production and blood-brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease.
Cytotherapy
; 14(8): 1011-21, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22809224
ABSTRACT
BACKGROUND AIMS:
Acute liver failure (ALF), although rare, remains a rapidly progressive and frequently fatal condition. Acetaminophen (APAP) poisoning induces a massive hepatic necrosis and often leads to death as a result of cerebral edema. Cell-based therapies are currently being investigated for liver injuries. We evaluated the therapeutic potential of transplantation of bone marrow mononuclear cells (BMC) in a mouse model of acute liver injury.METHODS:
ALF was induced in C57Bl/6 mice submitted to an alcoholic diet followed by fasting and injection of APAP. Mice were transplanted with 10(7) BMC obtained from enhanced green fluorescent protein (GFP) transgenic mice.RESULTS:
BMC transplantation caused a significant reduction in APAP-induced mortality. However, no significant differences in serum aminotransferase concentrations, extension of liver necrosis, number of inflammatory cells and levels of cytokines in the liver were found when BMC- and saline-injected groups were compared. Moreover, recruitment of transplanted cells to the liver was very low and no donor-derived hepatocytes were observed. Mice submitted to BMC therapy had some protection against disruption of the blood-brain barrier, despite their hyperammonemia, and serum metalloproteinase (MMP)-9 activity similar to the saline-injected group. Tumor necrosis factor (TNF)-α concentrations were decreased in the serum of BMC-treated mice. This reduction was associated with an early increase in interleukin (IL)-10 mRNA expression in the spleen and bone marrow after BMC treatment.CONCLUSIONS:
BMC transplantation protects mice submitted to high doses of APAP and is a potential candidate for ALF treatment, probably via an immunomodulatory effect on TNF-α production.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Medula Óssea
/
Fator de Necrose Tumoral alfa
/
Falência Hepática Aguda
/
Necrose Hepática Massiva
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cytotherapy
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Brasil