P0118 : Phase 1–2 clinical trial in patients with decompensated liver cirrhosis treated with bone-marrow derived endothelial progenitor cells

From the Liver Unit and CIBERehd Pamplona, Spain; Centro de Inve Enfermedades Hep aticas y Dig Spain; Instituto de Investigaci on Pamplona, Spain; Hepatology Investigaci on M edica Aplicada Hematology and Cell Therapy, C Pamplona, Spain; Interventional R Navarra, Pamplona, Spain. 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 functionandhepatic venouspressuregradient (HVPG)and their relation with the characteristics of the cellular product were analyzed. Twelve patients withChild-Pugh$8 liver cirrhosis underwentbonemarrowharvest forexvivodifferentiationof EPC. Thefinalproductwasadministered through thehepaticartery inasingle 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 (P0.042) in thefirst 90daysaftercellsadministrationand5of the9patients aliveat90days showedadecreasedofHVPG. Therewasadirectcorrelationbetween the expression of acetylated-low density lipoprotein and vonWillebrand 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 EPCshowedan improvementof liver functionandportal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation. (Translational Research 2016;-:1–12)