title: Nitric oxide augments mesenchymal stem cell ability to repair liver fibrosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Gibran
authors.initials: G
authors.lastname: Ali
authors.forename: Sadia
authors.initials: S
authors.lastname: Mohsin
authors.forename: Mohsin
authors.initials: M
authors.lastname: Khan
authors.forename: Ghazanfar Ali
authors.initials: GA
authors.lastname: Nasir
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Shams
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D003094:Collagen