title: Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
abstract: Mesenchymal stromal cell (MSC) infusion could be a means to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase I study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients.
  
  
  
  Ten liver transplant recipients under standard immunosuppression received 1.5-3×106/kg third-party unrelated MSCs on postoperative day 3±2, and were prospectively compared to a control group of ten liver transplant recipients. As primary endpoints, MSC infusion toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary endpoints, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients.
  
  
  
  No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary endpoints, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful.
  
  
  
  No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients.
  
  
  
  Therapy with mesenchymal stromal cells (MSCs) has been proposed as a means to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in ten liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression.
  
  
  
  Eudract: # 2011-001822-81, ClinicalTrials.gov: # NCT 01429038.
authors.affiliation: Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, (CHU ULg), Belgium; Mesenchymal stromal cell In Solid Organ Transplantation (MISOT) consortium(1). Electronic address: olivier.detry@transplantation.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Detry
authors.affiliation: Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, (CHU ULg), Belgium; Mesenchymal stromal cell In Solid Organ Transplantation (MISOT) consortium(1).
authors.forename: Morgan
authors.initials: M
authors.lastname: Vandermeulen
authors.affiliation: Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Delbouille
authors.affiliation: Department of Pathology, CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Joan
authors.initials: J
authors.lastname: Somja
authors.affiliation: Department of Pathology, CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Noella
authors.initials: N
authors.lastname: Bletard
authors.affiliation: Laboratory of Cell and Gene Therapy (LTCG), CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Briquet
authors.affiliation: Laboratory of Cell and Gene Therapy (LTCG), CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Lechanteur
authors.affiliation: Laboratory of Cell and Gene Therapy (LTCG), CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Giet
authors.affiliation: Laboratory of Cell and Gene Therapy (LTCG), CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Baudoux
authors.affiliation: Interdisciplinary Cluster for Applied Genoproteomics (GIGA)-I3-haematology, University of Liege, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Hannon
authors.affiliation: Interdisciplinary Cluster for Applied Genoproteomics (GIGA)-I3-haematology, University of Liege, Belgium; Department of Haematology, CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Baron
authors.affiliation: Interdisciplinary Cluster for Applied Genoproteomics (GIGA)-I3-haematology, University of Liege, Belgium; Department of Haematology, CHU Liege, University of Liege, (CHU ULg), Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D006801:Humans; D016031:Liver Transplantation; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
keywords: Cancer; Cell therapy; Cirrhosis; Hepatic insufficiency; Immune tolerance; Liver diseases; Liver failure; MISOT; Mesenchymal stem cells; Stem cells