Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress.
AIM
To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage.


METHODS
Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay.


RESULTS
CD11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin.


CONCLUSION
Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.
['de Souza|Veruska Cintia Alexandrino|VCA|', 'Pereira|Thiago Almeida|TA|', 'Teixeira|Valéria Wanderley|VW|', 'Carvalho|Helotonio|H|', 'de Castro|Maria Carolina Accioly Brelaz|MCAB|', "D'assunção|Carolline Guimarães|CG|", 'de Barros|Andréia Ferreira|AF|', 'Carvalho|Camila Lima|CL|', 'de Lorena|Virgínia Maria Barros|VMB|', 'Costa|Vláudia Maria Assis|VMA|', 'Teixeira|Álvaro Aguiar Coelho|ÁAC|', 'Figueiredo|Regina Celia Bressan Queiroz|RCBQ|', 'de Oliveira|Sheilla Andrade|SA|']
D000199:Actins D000818:Animals D039481:CD11b Antigen D002251:Carbon Tetrachloride D002469:Cell Separation D064987:Cell- and Tissue-Based Therapy D016207:Cytokines D004195:Disease Models, Animal D004797:Enzyme-Linked Immunosorbent Assay D000431:Ethanol D005434:Flow Cytometry D005978:Glutathione D006801:Humans D007150:Immunohistochemistry D018950:Lipopolysaccharide Receptors D008099:Liver D008103:Liver Cirrhosis D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009000:Monocytes D053495:Osteopontin D018384:Oxidative Stress
Monocytes Liver fibrosis Glutathione Bone marrow mononuclear cells Cell therapy Macrophages