Nitric oxide augments mesenchymal stem cell ability to repair liver fibrosis

• Published in: Journal of translational medicine 2012-04, Vol.10 (1), p.75-75, Article 75
• Main Authors: Ali, Gibran, Mohsin, Sadia, Khan, Mohsin, Nasir, Ghazanfar Ali, Shams, Sulaiman, Khan, Shaheen N, Riazuddin, Sheikh
• Format: Article
• Language: English
• Subjects: Albumin; Analysis; Animals; Apoptosis; Bilirubin; Biomedical research; Cell Lineage - drug effects; Cell Movement - drug effects; Cellular Microenvironment - drug effects; Collagen; Collagen - metabolism; Cyanides; Development and progression; Female; Fibrosis; Gene expression; Gene Expression Profiling; Hepatic stellate cells (HSCs); Keratin; Laboratory animals; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cirrhosis; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Liver diseases; Liver fibrosis; Mesenchymal stem cells (MSCs); Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Nitric oxide; Nitric Oxide - metabolism; Nitroprusside - pharmacology; Phosphatases; Physiological aspects; Recovery of Function - drug effects; Rodents; Sodium nitroferricyanide; Stem cells; Transplantation; Wound healing; Wound Healing - drug effects
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-10-75

Liver fibrosis is a major health problem worldwide and poses a serious obstacle for cell based therapies. Mesenchymal stem cells (MSCs) are multipotent and important candidate cells for future clinical applications however success of MSC therapy depends upon their homing and survival in recipient organs. This study was designed to improve the repair potential of MSCs by transplanting them in sodium nitroprusside (SNP) pretreated mice with CCl(4) induced liver fibrosis. SNP 100 mM, a nitric oxide (NO) donor, was administered twice a week for 4 weeks to CCl(4)-injured mice. MSCs were isolated from C57BL/6 wild type mice and transplanted in the left lateral lobe of the liver in experimental animals. After 4 weeks, animals were sacrificed and liver improvement was analyzed. Analysis of fibrosis by qRT-PCR and sirius red staining, homing, bilirubin and alkaline phosphatase (ALP) serum levels between different treatment groups were compared to control. Liver histology demonstrated enhanced MSCs homing in SNP-MSCs group compared to MSCs group. The gene expression of fibrotic markers; αSMA, collagen 1α1, TIMP, NFκB and iNOS was down regulated while cytokeratin 18, albumin and eNOS was up-regulated in SNP-MSCs group. Combine treatment sequentially reduced fibrosis in SNP-MSCs treated liver compared to the other treatment groups. These results were also comparable with reduced serum levels of bilirubin and ALP observed in SNP-MSCs treated group. This study demonstrated that NO effectively augments MSC ability to repair liver fibrosis induced by CCl(4) in mice and therefore is a better treatment regimen to reduce liver fibrosis.