Adult derived mononuclear bone marrow cells improve survival in a model of acetaminophen-induced acute liver failure in rats

• DOI: 10.1016/j.tox.2008.01.015
• Publication Date: 2008-02-02T12:24:01Z
• Authors: Maria Cristina Be...; Fernanda Pereira; Guilherme Baldo; Ângela Maria Vice...; Carlos Oscar Kieling; Themis Reverbel d...; Luise Meurer; Marcos Eugênio So...; Roberto Giugliani; Ursula Matte
• Keywords: Male; 0303 health sciences; Analgesics, Non-Narcotic; Liver Failure, Acute; Rats; 3. Good health; Survival Rate; Disease Models, Animal; 03 medical and health sciences; Liver; Animals; Ficoll; Female; Rats, Wistar; Acetaminophen; Bone Marrow Transplantation

Acute liver failure (ALF) is characterized by a rapid loss of hepatic function, with high mortality. Acetaminophen (APAP) intoxication and viral hepatitis are common causes of ALF. Several studies have shown the capacity of adult bone marrow cells to differentiate in hepatocytes, suggesting their use for treating ALF.In the present study, we tested the use of adult derived mononuclear bone marrow fraction to improve the survival of Wistar rats with APAP-induced ALF.Forty-eight female Wistar rats pre-induced with phenobarbital were given APAP in a single dose of 1g/kg via intraperitoneal injection. Bone marrow mononuclear cells were purified from male rats using FICOLL gradient and injected through the portal vein in a volume of 0.2mL containing 1x10(6) cells stained with DAPI. Treatment was administered 24h after APAP injection. The sham group (n=24), received 0.2mL of saline through the portal vein 24h after APAP administration. Survival, liver histology and ALT levels were observed.Survival 72h post-APAP administration was 33% in the sham group and 70.8% in the group receiving bone marrow cells. Liver histology in treated animals showed less intense necrosis and the presence of DAPI-positive cells.We have shown that bone marrow derived cells are capable of significantly increasing the survival rate of APAP-induced ALF in 37.5% (95% CI, 27.8-40.3%).