title: Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.
abstract: Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50-62 2017 AASLD.
authors: Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe and Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia.|Gene Therapy Unit, Pharmacology Department, Medicine Faculty, Universidad de Valencia, Valencia, Spain.
authors: Luis
authors: L
authors: Sendra Gisbert
authors: Gene Therapy Unit, Pharmacology Department, Medicine Faculty, Universidad de Valencia, Valencia, Spain.
authors: Antonio
authors: A
authors: Miguel Matas
authors: General and Digestive Surgery Department, Hospital Clínico Universitario, Valencia, Spain.
authors: Luis
authors: L
authors: Sabater Ortí
authors: Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe and Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia.
authors: María José
authors: 0000-0002-6042-4185
authors: MJ
authors: Herrero
authors: Fibrosis Laboratory, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Laura
authors: L
authors: Sabater Olivas
authors: Hepatobiliopancreatic Surgery and Transplantation Unit, General Surgery Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Eva María
authors: EM
authors: Montalvá Orón
authors: Coloproctology Unit, General Surgery Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Matteo
authors: M
authors: Frasson
authors: Intenanomat S.L., Valencia, Spain.
authors: Rafael
authors: R
authors: Abargues López
authors: Hepatobiliopancreatic Surgery and Transplantation Unit, General Surgery Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Rafael
authors: R
authors: López-Andújar
authors: Coloproctology Unit, General Surgery Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Eduardo
authors: E
authors: García-Granero Ximénez
authors: Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe and Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia.|Gene Therapy Unit, Pharmacology Department, Medicine Faculty, Universidad de Valencia, Valencia, Spain.
authors: Salvador Francisco
authors: SF
authors: Aliño Pellicer
mesh_terms: D064591:Allografts / Q000276:immunology / Q000378:metabolism; D058625:End Stage Liver Disease / Q000601:surgery*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006046:Gold / Q000737:chemistry; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D016031:Liver Transplantation / Q000009:adverse effects*; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000737:chemistry; D046509:Tissue Culture Techniques; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D006046:Gold