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

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...

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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)
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cited_by cdi_FETCH-LOGICAL-c725t-785b1c119a5d9142e14747864d120f6cd967cd56d0e8ab9f91b4516cc355957a3
cites cdi_FETCH-LOGICAL-c725t-785b1c119a5d9142e14747864d120f6cd967cd56d0e8ab9f91b4516cc355957a3
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container_issue 12
container_start_page e0166849
container_title PloS one
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creator Meza-Ríos, Alejandra
García-Benavides, Leonel
García-Bañuelos, Jesus
Salazar-Montes, Adriana
Armendáriz-Borunda, Juan
Sandoval-Rodríguez, Ana
description 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.
doi_str_mv 10.1371/journal.pone.0166849
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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. 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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)
title Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis
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