title: Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.
abstract: OBJECTIVE
  hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model.
  
  
  METHODS
  hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin.
  
  
  RESULTS
  hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group.
  
  
  CONCLUSIONS
  These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.
authors.affiliation: Institute for Molecular Biology in Medicine, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Meza-Ríos
authors.affiliation: Unit of Cardiovascular Investigation, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Leonel
authors.initials: L
authors.lastname: García-Benavides
authors.affiliation: Institute for Molecular Biology in Medicine, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: García-Bañuelos
authors.affiliation: Institute for Molecular Biology in Medicine, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Salazar-Montes
authors.affiliation: Institute for Molecular Biology in Medicine, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.|INNOVARE, Guadalajara, Jalisco, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.affiliation: Institute for Molecular Biology in Medicine, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Ana
authors.initials: A
authors.lastname: Sandoval-Rodríguez
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D014568:Urokinase-Type Plasminogen Activator