title: Bone marrow cell transplantation is associated with fibrogenic cells apoptosis during hepatic regeneration in cholestatic rats.
abstract: Liver fibrosis is accompanied by hepatocyte death and proliferation of α-SMA(+) fibrogenic cells (activated hepatic stellate cells and myofibroblasts), which synthesize extracellular matrix components that contribute to disorganization of the hepatic parenchyma and loss of liver function. Therefore, apoptosis of these fibrogenic cells is important to hepatic regeneration. This study aimed to analyze the effect of cell therapy using bone marrow mononuclear cell (BMMNC) transplantation on α-SMA expression and on apoptosis of hepatic cells during liver fibrosis induced by bile duct ligation (BDL). Livers were collected from normal rats, fibrotic rats after 14 and 21 days of BDL, and rats that received BMMNC at 14 days of BDL and were analyzed after 7 days. Apoptosis in fibrogenic cells was analyzed by immunoperoxidase, confocal microscopy, and Western blotting, and liver regeneration was assessed by proliferating cell nuclear antigen staining. Results showed that caspase-3 and proliferating cell nuclear antigen expression were significantly increased in the BMMNC-treated group. Additionally, confocal microscopy analysis showed cells coexpressing α-SMA and caspase-3 in these animals, suggesting fibrogenic cell death. These results suggest a novel role for BMMNC in liver regeneration during fibrotic disease by stimulating fibrogenic cells apoptosis and hepatocyte proliferation, probably through secretion of specific cytokines that modulate the hepatic microenvironment toward an antifibrogenic balance.
authors.affiliation: Laboratório Cultura de Células, Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, RJ, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Nunes de Carvalho
authors.forename: Dalvaci
authors.initials: D
authors.lastname: da Cunha Lira
authors.forename: Erika Afonso
authors.initials: EA
authors.lastname: Costa Cortez
authors.forename: Daniela Caldas
authors.initials: DC
authors.lastname: de Andrade
authors.forename: Alessandra Alves
authors.initials: AA
authors.lastname: Thole
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Stumbo
authors.forename: Lais
authors.initials: L
authors.lastname: de Carvalho
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001652:Bile Ducts / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000199:Actins; D034961:Antigens, Nuclear; D015415:Biomarkers; D053148:Caspase 3; C498862:Acta2 protein, rat