European Radiology

, Volume 26, Issue 1, pp 95–102 | Cite as

Human AAT gene transfer to pig liver improved by using a perfusion isolated organ endovascular procedure

  • Luis Sendra
  • Daniel Pérez
  • Antonio Miguel
  • María José Herrero
  • Inmaculada Noguera
  • Ana Díaz
  • Domingo Barettino
  • Luis Martí-Bonmatí
  • Salvador F. Aliño
Interventional
First Online:
Received:
Revised:
Accepted:

Abstract

Objective

The efficiency of endovascular liver gene transfer in pigs is evaluated by comparing two models of retrograde catheterization: single lobe catheterization with portal inflow (open procedure) versus whole liver isolation with portal and inferior vena cava blockage (close procedure).

Methods

Percutaneous endovascular catheterization was performed in pigs. Open procedure (n = 3): 8Fr balloon catheter placement in a suprahepatic branch through the jugular vein. Closed procedure (n = 3): simultaneous catheterization of the intrahepatic portal vein (transhepatic catheterization, 10Fr balloon catheter), the supra- and infrahepatic cava veins (8Fr balloon catheters through the jugular and femoral veins). In both models, 200 ml of hAAT DNA solution (20 μg/ml) were retrogradely injected at 20 ml/s. Tissue samples (8 per liver) were obtained 14 days later and the exogenous DNA, RNA and protein per cell were quantified. Blood samples were collected periodically for transaminase determination in all the animals.

Results

The open procedure achieved lower (approx. 1000-fold) DNA delivery, resulting in a significantly lower (p < 0.001) gene transcription (>100-fold). The closed model also achieved a higher translation index, although differences were smaller (p < 0.001).

Conclusions

Portal inflow blockage increased the delivery, transcription and translation indexes, significantly improving the final procedure efficacy when compared with an open procedure.

Key Points

• Endovascular hydrodynamic pig liver gene transfer: open procedure versus closed procedure

• Open procedure resulted in much lower DNA delivery than closed model

• Open procedure reached significantly lower gene transcription index

• Translation index with closed model was higher than with the open

Keywords

Catheter Hydrodynamic Naked DNA Vascular exclusion Retrograde injection 
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Notes

Acknowledgments

We would like to thank David Hervás from the Biostatistics facility at El Instituto de Investigación Sanitaria (IIS) La Fe.

The scientific guarantor of this publication is Prof. Salvador F. Aliño. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study received funding by the Spanish Ministry of Economy and Competitiveness. Project reference: SAF2011-27002. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained.

Approval from the institutional animal care committee was obtained. Study subjects or cohorts have not been previously reported. Methodology: experimental, performed at one institution.

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Copyright information

© European Society of Radiology 2015

Authors and Affiliations

  • Luis Sendra
    • 1
  • Daniel Pérez
    • 2
  • Antonio Miguel
    • 1
  • María José Herrero
    • 1
    • 3
  • Inmaculada Noguera
    • 4
  • Ana Díaz
    • 4
  • Domingo Barettino
    • 5
  • Luis Martí-Bonmatí
    • 2
  • Salvador F. Aliño
    • 1
    • 3
    • 6
  1. 1.Departamento de Farmacología, Facultad de MedicinaUniversidad de ValenciaValenciaSpain
  2. 2.Servicio de Radiología, Hospital Universitario y Politécnico La Fe, Grupo de Investigación Biomédica de Imagen IIS La FeValenciaSpain
  3. 3.Unidad de Farmacogenética, IIS La Fe, Servicio de FarmaciaHospital Universitario y Politécnico La FeValenciaSpain
  4. 4.SCSIE, Servicio Central de Soporte a la Investigación ExperimentalUniversidad de ValenciaValenciaSpain
  5. 5.Instituto de Biomedicina de Valencia, CSICValenciaSpain
  6. 6.Unidad de Farmacología Clínica, ACM Hospital Universitario y Politécnico La FeValenciaSpain

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