1. Volumetric Portal Embolization
- Author
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Olivier Trassard, Frederic Kanso, Martin Gaillard, Guillaume Pourcher, Ibrahim Dagher, Hoda El-Kehdy, Istvan Blazsek, Anne Dubart-Kupperschmitt, Hélène Agostini, Marie-Thérèse Groyer-Picard, and Pharmaceutical and Pharmacological Sciences
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Cell Survival ,Polyesters ,medicine.medical_treatment ,graft survival ,Biomarkers/metabolism ,03 medical and health sciences ,0302 clinical medicine ,Liver/blood supply ,In vivo ,medicine ,Hepatectomy ,Distribution (pharmacology) ,Animals ,Embolization ,Ki-67 Antigen/metabolism ,Ligature ,Transplantation ,Portal Vein ,business.industry ,Regeneration (biology) ,Hepatocytes/metabolism ,Organ Size ,Portal Vein/diagnostic imaging ,Embolization, Therapeutic ,Liver regeneration ,Microspheres ,Liver Regeneration ,Mice, Inbred C57BL ,Ki-67 Antigen ,medicine.anatomical_structure ,Liver ,Cell Tracking ,030220 oncology & carcinogenesis ,Hepatocyte ,Injections, Intravenous ,Hepatocytes ,Polyesters/administration & dosage ,030211 gastroenterology & hepatology ,Female ,business ,Embolization, Therapeutic/methods ,Hepatectomy/methods ,Biomarkers ,radiography - Abstract
Background Hepatocyte transplantation has been proposed as an alternative to orthotopic liver transplantation to treat metabolic liver diseases. This approach requires preconditioning of the host liver to enhance engraftment of transplanted hepatocytes. Different methods are currently used in preclinical models: partial hepatectomy, portal ligature or embolization, and radiotherapy or chemotherapeutic drugs. However, these methods carry high risks of complications and are problematic for use in clinical practice. Here, we developed an innovative method called volumetric (distal, partial, and random) portal embolization (VPE), which preserves total liver volume. Methods Embolization was performed in the portal trunk of C57BL6 adult mice with polyester microspheres, to ensure a bilateral and distal distribution. The repartition of microspheres was studied by angiographic and histological analyses. Liver regeneration was evaluated by Ki67 labeling. Optimal conditions for VPE were determined, and the resulting regeneration was compared with that after partial hepatectomy (70%). Labeled adult hepatocytes were then transplanted, and engraftment was compared between embolized (n = 19) and nonembolized mice (n = 8). Engraftment was assessed in vivo and histologically by tracking labeled cells at day 5. Results The best volumetric embolization conditions, which resulted in the regeneration of 5% of total liver, were 8 × 10 ten-micron microspheres infused with a 29 G needle directly into the portal trunk at 3.3 μL/s. In these conditions, transplanted hepatocytes engraftment was significantly higher than that in control conditions (3 vs 0.65%). Conclusions The VPE is a new, minimally invasive, and efficient technique to prepare the host liver for cell transplantation.
- Published
- 2016