Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl4 - induced liver fibrosis in mice

• Published in: Biomedicine & pharmacotherapy 2017-05, Vol.89, p.1378-1386
• Main Authors: Elmahdy, Nageh Ahmed, Sokar, Samia Salem, Salem, Mohamed Labib, Sarhan, Naglaa Ibrahim, Abou-Elela, Sherin Hamed
• Format: Article
• Language: English
• Subjects: Anti-inflammatory; Antifibrotic; Human umbilical cord mononuclear cells; Internal Medicine; Liver fibrosis; Medical Education; Mouse bone marrow cells; Sylimarin
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.03.007

Abstract Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4 ) induced liver fibrosis in mice and compare it with that of silymarin. In the present study, male albino mice (N = 60) were divided into six groups (10 mice each), the first group served as the normal control group while the remaining five groups were rendered fibrotic by intraperitoneal injections of CCl4 and being left for 6 weeks to develop hepatic fibrosis. Thereafter, the mice were divided into CCl4 group, CCl4 group receiving MNC or BMC or silymarin or MNC and silymarin combination. After the specified treatment period, animals were then euthanized, blood and tissue samples were collected for measurement of alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), reduced glutathione(GSH), collagen, Laminin, transforming growth factor β1(TGFβ1), tumor necrosis factor alpha(TNFα). MNC, BMC, and the combination therapy showed a significant decrease in ALT, AST, MDA, collagen, Laminin, TGFβ1, and TNFα and a significant increase in GSH. The data displayed a similar regression of fibrosis with the histological and immunohistological parameters. In conclusion, MNC, BMC and the combination therapy showed a potential therapeutic effect against liver fibrosis via reducing oxidative stress, inflammatory mediators, and fibrogenic markers.