Published online Jul 28, 2017. doi: 10.3748/wjg.v23.i28.5146
Peer-review started: January 4, 2017
First decision: February 9, 2017
Revised: February 22, 2017
Accepted: April 12, 2017
Article in press: April 12, 2017
Published online: July 28, 2017
Processing time: 209 Days and 9.3 Hours
To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage.
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.
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.
Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.
Core tip: Chronic inflammation is now recognized as a central player in the development of liver fibrosis. Studies have shown that activated macrophages establish a link between chronic inflammation and fibrosis in various organs. The present study evaluated the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of liver damage. The results show that mice with transplants had improvement of liver fibrosis by way of a reduction in oxidative stress and inflammation and an increase in anti-fibrogenic factors. The study demonstrates the beneficial effects of cellular therapy in liver fibrosis and also reports on the important modulatory mechanisms involved.