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- Title
Human AAT gene transfer to pig liver improved by using a perfusion isolated organ endovascular procedure.
- Authors
Sendra, Luis; Pérez, Daniel; Miguel, Antonio; Herrero, María; Noguera, Inmaculada; Díaz, Ana; Barettino, Domingo; Martí-Bonmatí, Luis; Aliño, Salvador; Herrero, María José; Aliño, Salvador F
- Abstract
<bold>Objective: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>Portal inflow blockage increased the delivery, transcription and translation indexes, significantly improving the final procedure efficacy when compared with an open procedure.<bold>Key Points: </bold>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.
- Subjects
GENETIC transformation; LIVER; LABORATORY swine; ISOLATION perfusion; ENDOVASCULAR surgery; HYDRODYNAMICS; DNA; CATHETERS; LIVER disease treatment; ANIMAL experimentation; CARRIER proteins; GENE therapy; GENETIC techniques; PERFUSION; SWINE
- Publication
European Radiology, 2016, Vol 26, Issue 1, p95
- ISSN
0938-7994
- Publication type
journal article
- DOI
10.1007/s00330-015-3792-2