Abstract
Purpose To investigate the use of percutaneous catheter-based techniques for portal vein application of AD-MSCs in a porcine model of cirrhosis. Materials and Methods Eleven pigs received iodized oil and ethanol into the hepatic artery to induce liver injury. AD-MSCs were harvested from the animals’ cervical region. AD-MSCs were genetically engineered to express green fluorescent protein (GFP) using the piggyBac transposon. Percutaneous access was gained into a peripheral portal branch and a 6-French balloon occlusion catheter was positioned into the main portal vein for cell delivery. Six experimental animals received portal application of AD-MSCs. Cells were allowed to dwell for 10 minutes. Five control animals received a sham injection of normal saline into the portal vein. Hepatic venous pressure gradient (HVPG) was measured before and after cell delivery. Percutaneous liver biopsies were obtained 2 hours after cell application. All animals were euthanized within four weeks of cell administration. Presence and distribution of cells was assessed with fluorescent microscopy in biopsy and necropsy specimens. Results Cirrhosis was successfully induced in all animals. 60-100 million AD-MSCs were successfully delivered into the portal vein in all experimental animals. Cells were delivered with the aid of a balloon-occlusion catheter, in order to cessate portal venous inflow during administration, a maneuver used to minimize washout of delivered cells into the systemic circulation. Cell application was not associated with complications. Specifically, no incidents of portal thrombosis or hypertension were observed after delivery. GFP-expressing AD-MSCs were visualized by fluorescent microscopy in biopsy specimens obtained 2 hours after application and were distributed primarily within the sinusoidal spaces. Four weeks after implantation, AD-MSCs were not identified in the histological specimens. Conclusion Using percutaneous catheter-based techniques, AD-MSCs can be safely administered into the portal vein in a porcine model. Mesenchymal stem cells distributed primarily into the sinusoidal spaces in the acute implantation period. Engraftment of the AD-MDSCs was not visualized after 4 weeks.
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