title: Phase 1-2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells.
abstract: The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation.
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. Electronic address: ddavola@unav.es.
authors.forename: Delia
authors.initials: D
authors.lastname: D'Avola
authors.affiliation: Hepatology and Gene Therapy, Centro Investigación Médica Aplicada (CIMA), Pamplona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Fernández-Ruiz
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carmona-Torre
authors.affiliation: Hepatology and Gene Therapy, Centro Investigación Médica Aplicada (CIMA), Pamplona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Méndez
authors.affiliation: Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-Calvo
authors.affiliation: Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.affiliation: Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Andreu
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Herrero
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñarrairaegui
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fuertes
authors.affiliation: Interventional Radiology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Bilbao
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Hepatology and Gene Therapy, Centro Investigación Médica Aplicada (CIMA), Pamplona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Liver Unit and CIBERehd, Clínica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Quiroga
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells; D066026:Endothelial Progenitor Cells / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000628:therapy*; D008104:Liver Cirrhosis, Alcoholic / Q000628:therapy; D017093:Liver Failure; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects