title: Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo.
abstract: OBJECTIVE
  To overcome current limitations of therapy for liver diseases, cell-based therapies using mesenchymal stem cells (MSC) have been attempted through basic and clinical approaches. Oxidative stress is a crucial factor in hepatology, and reactive oxygen species (ROS) are well-established molecules responsible for its deleterious effects. The antioxidant properties of MSC were recently demonstrated, and therefore we examined the antioxidant activity of canine MSC (cMSC), their effects on isolated hepatocytes in vitro and their curative potential against thioacetamide (TAA)-induced liver injury in vivo.
  
  
  METHODS
  To evaluate the ability of cMSC to challenge oxidative stress, cell viability, cytotoxicity and ROS were measured in cultured cMSC treated with TAA. Also, cMSC were co-cultured with hepatocytes in the same injury condition, and the ROS level was measured exclusively in hepatocytes. Finally, to verify the curative potential of cMSC, 2.0 × 10(6) cells or phosphate-buffered saline were injected systemically in non-obese diabetic/severe combined immunodeficiency mice that received TAA injections twice a week for 13 weeks. We then evaluated histological parameters, serum injury markers and redox homeostasis.
  
  
  RESULTS
  cMSC overcame TAA-induced oxidative stress in vitro, as shown by increased viability and lower cytotoxicity and ROS levels. Moreover, hepatocytes co-cultured with cMSC also showed decreased cellular ROS. The in vivo study showed that mice treated with cMSC presented with an ameliorated histological pattern, suppressed fibrosis, lower serum injury marker levels and better oxidative parameters.
  
  
  CONCLUSIONS
  We concluded that cMSC injection reduce TAA-induced liver injury through antioxidant activities and hepatoprotective effects, showing a curative potential in liver diseases.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan; Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Quintanilha
authors.forename: Taro
authors.initials: T
authors.lastname: Takami
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirose
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Murata
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Regina Coeli Dos Santos
authors.initials: RC
authors.lastname: Goldenberg
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
keywords: NF-E2-related factor 2; liver; mesenchymal stem cells; oxidative stress; reactive oxygen species