title: Adult derived mononuclear bone marrow cells improve survival in a model of acetaminophen-induced acute liver failure in rats.
abstract: 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%).
authors.affiliation: Gene Therapy Center, Research Center, Hospital de Clinicas, Porto Alegre, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Belardinelli
authors.forename: Fernanda
authors.initials: F
authors.lastname: Pereira
authors.forename: Guilherme
authors.initials: G
authors.lastname: Baldo
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Vicente Tavares
authors.forename: Carlos Oscar
authors.initials: CO
authors.lastname: Kieling
authors.forename: Themis Reverbel
authors.initials: TR
authors.lastname: da Silveira
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Marcos Eugênio
authors.initials: ME
authors.lastname: Soares Duarte
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
mesh_terms: 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
chemical_list: D018712:Analgesics, Non-Narcotic; D005362:Ficoll; D000082:Acetaminophen