title: Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury.
abstract: The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 x 10(7) cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriana B
authors.initials: AB
authors.lastname: Carvalho
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Quintanilha
authors.forename: Juliana V
authors.initials: JV
authors.lastname: Dias
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Paredes
authors.forename: Elida G
authors.initials: EG
authors.lastname: Mannheimer
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Carvalho
authors.forename: Karina D
authors.initials: KD
authors.lastname: Asensi
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.forename: Lea Mirian B
authors.initials: LM
authors.lastname: Fonseca
authors.forename: Celia Maria C
authors.initials: CM
authors.lastname: Resende
authors.forename: Guilherme F M
authors.initials: GF
authors.lastname: Rezende
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Antonio Carlos Campos
authors.initials: AC
authors.lastname: de Carvalho
authors.forename: Regina C S
authors.initials: RC
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D007267:Injections; D008107:Liver Diseases / Q000473:pathology* / Q000503:physiopathology*; D008111:Liver Function Tests; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology*; D015609:Organotechnetium Compounds; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D015415:Biomarkers; D015609:Organotechnetium Compounds; D003094:Collagen