Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis

• Published in: PloS one 2016-12, Vol.11 (12), p.e0166849-e0166849
• Main Authors: Meza-Ríos, Alejandra, García-Benavides, Leonel, García-Bañuelos, Jesus, Salazar-Montes, Adriana, Armendáriz-Borunda, Juan, Sandoval-Rodríguez, Ana
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Albumin; Animals; Biology and Life Sciences; Care and treatment; Cell Differentiation; Chemokines; Cirrhosis; Collagen; Combinatorial analysis; Combined Modality Therapy; Connective tissue growth factor; Control; Data collection; Dependovirus - genetics; Fibrosis; Gelatinase A; Gene expression; Gene therapy; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genomics; Growth factors; Health sciences; Humans; Liver; Liver cirrhosis; Liver Cirrhosis, Experimental - genetics; Liver Cirrhosis, Experimental - therapy; Liver transplants; Male; Medicine; Medicine and Health Sciences; Molecular biology; mRNA; Rats; Rats, Wistar; Regeneration; Research and Analysis Methods; Serum levels; Stem cells; Stromal Cells - transplantation; Studies; Tissue transplantation; Transforming growth factor-b1; Transplantation; Transplants & implants; Treatment Outcome; Urokinase-Type Plasminogen Activator - genetics; Vectors (Biology)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166849

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. 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. 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. 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.