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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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%).
Belardinelli
Maria Cristina
MC
Gene Therapy Center, Research Center, Hospital de Clinicas, Porto Alegre, Brazil.
Pereira
Fernanda
F
Baldo
Guilherme
G
Vicente Tavares
Angela Maria
AM
Kieling
Carlos Oscar
CO
da Silveira
Themis Reverbel
TR
Meurer
Luise
L
Soares Duarte
Marcos Eugênio
ME
Giugliani
Roberto
R
Matte
Ursula
U
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D005260:Female; D005362:Ficoll; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
D018712:Analgesics, Non-Narcotic; D005362:Ficoll; D000082:Acetaminophen