title: Volumetric Portal Embolization: A New Concept to Improve Liver Regeneration and Hepatocyte Engraftment.
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.
authors.affiliation: 1 INSERM U972, Paul Brousse Hospital, Villejuif, France. 2 UMR_S 972, Faculté de Médecine Paris-Sud, Kremlin Bicêtre, France. 3 DHU Hepatinov, Paul Brousse Hospital, Villejuif, France. 4 Institut Biomédical Bicêtre IFR93, Bicêtre Hospital, Kremlin-Bicêtre, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pourcher
authors.forename: Hoda
authors.initials: H
authors.lastname: El-Kehdy
authors.forename: Frederic
authors.initials: F
authors.lastname: Kanso
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Groyer-Picard
authors.forename: Martin
authors.initials: M
authors.lastname: Gaillard
authors.forename: Olivier
authors.initials: O
authors.lastname: Trassard
authors.forename: Istvan
authors.initials: I
authors.lastname: Blazsek
authors.forename: Hélène
authors.initials: H
authors.lastname: Agostini
authors.forename: Anne
authors.initials: A
authors.lastname: Dubart-Kupperschmitt
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Dagher
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D058948:Cell Tracking; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006085:Graft Survival; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D007275:Injections, Intravenous; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009929:Organ Size; D011091:Polyesters / Q000008:administration & dosage*; D011169:Portal Vein / Q000000981:diagnostic imaging; D011859:Radiography; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D011091:Polyesters