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Canine mesenchymal stem cells show antioxidant properties against thioacetamide‐induced liver injury in vitro and in vivo
Author(s) -
Quintanilha Luiz Fernando,
Takami Taro,
Hirose Yoshikazu,
Fujisawa Koichi,
Murata Yasuhiko,
Yamamoto Naoki,
Goldenberg Regina Coeli dos Santos,
Terai Shuji,
Sakaida Isao
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12204
Subject(s) - oxidative stress , thioacetamide , reactive oxygen species , in vivo , antioxidant , pharmacology , mesenchymal stem cell , liver injury , viability assay , chemistry , in vitro , biology , biochemistry , microbiology and biotechnology
Aim 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. Conclusion We concluded that cMSC injection reduce TAA ‐induced liver injury through antioxidant activities and hepatoprotective effects, showing a curative potential in liver diseases.