Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl4- induced liver fibrosis in mice.
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 CCl4and being left for 6 weeks to develop hepatic fibrosis. Thereafter, the mice were divided into CCl4group, CCl4group 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.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Nageh Ahmed
NA
Elmahdy
Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Samia Salem
SS
Sokar
Zoology Department, Faculty of Science, Immunology and Biotechnology Unit, Immunology and Biotechnology Division, Center of Excellence in Cancer Research, Tanta University, Tanta, Egypt.
Mohamed Labib
ML
Salem
Histology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Naglaa Ibrahim
NI
Sarhan
Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: sherin.hamed@gmail.com.
Sherin Hamed
SH
Abou-Elela
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology* / Q000378:metabolism
D007797:Laminin; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D003094:Collagen; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
Anti-inflammatory; Antifibrotic; Human umbilical cord mononuclear cells; Liver fibrosis; Mouse bone marrow cells; Sylimarin