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


ABSTRACT:

Background and aims

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-?I, TGF-?1, CTGF, ?-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 ?1, CTGF and ?-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.

SUBMITTER: Meza-Rios A 

PROVIDER: S-EPMC5161330 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

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

Meza-Ríos Alejandra A   García-Benavides Leonel L   García-Bañuelos Jesus J   Salazar-Montes Adriana A   Armendáriz-Borunda Juan J   Sandoval-Rodríguez Ana A  

PloS one 20161216 12


<h4>Background and aims</h4>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.<h4>Methods</h4>hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24  ...[more]

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