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

Autores de IIS La Fe

• Luis Sendra Gisbert

  Autor

• Daniel Pérez Enguix

  Autor

• Antonio Miguel Matas

  Autor

• María José Herrero Cervera

  Autor

• Inmaculada Noguera Salva

  Autor

• Domingo Barettino Fraile

  Autor

• 

  Luis Martí Bonmatí

  Autor

• Salvador F Aliño Pellicer

  Autor

Participantes ajenos a IIS La Fe

• Díaz A

Grupos

• Farmacogenética

• Investigacion Biomédica en Imagen (GIBI 2-30)

Abstract

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). 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 mu g/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. 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). Portal inflow blockage increased the delivery, transcription and translation indexes, significantly improving the final procedure efficacy when compared with an open procedure. aEuro cent Endovascular hydrodynamic pig liver gene transfer: open procedure versus closed procedure aEuro cent Open procedure resulted in much lower DNA delivery than closed model aEuro cent Open procedure reached significantly lower gene transcription index aEuro cent Translation index with closed model was higher than with the open.

Keywords

• Catheter; Hydrodynamic; Naked DNA; Vascular exclusion; Retrograde injection