Reference : Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I...
Scientific journals : Article
Human health sciences : Surgery
Human health sciences : Hematology
Human health sciences : Gastroenterology & hepatology
http://hdl.handle.net/2268/209463
Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
English
DETRY, Olivier mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie abdo, sénologique, endocrine et de transplantation >]
VANDERMEULEN, Morgan mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie abdo, sénologique, endocrine et de transplantation >]
DELBOUILLE, Marie-Hélène mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie abdo, sénologique, endocrine et de transplantation >]
SOMJA, Joan mailto [Centre Hospitalier Universitaire de Liège - CHU > > Service dermatopathologie >]
BLETARD, Noëlla mailto [Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques >]
Briquet, Alexandra mailto [Université de Liège > > GIGA-R : Hématologie >]
LECHANTEUR, Chantal mailto [Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire >]
GIET, Olivier mailto [Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire >]
BAUDOUX, Etienne mailto [Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire >]
Hannon, Muriel mailto [Université de Liège > > GIGA-R : Hématologie >]
Baron, Frédéric mailto [Université de Liège > > GIGA-R : Hématologie >]
Beguin, Yves mailto [Université de Liège > > GIGA-R : Hématologie >]
Jul-2017
Journal of Hepatology
67
1
47-55
Yes (verified by ORBi)
International
0168-8278
1600-0641
Netherlands
[en] Cancer ; Cell therapy ; Cirrhosis ; Hepatic insufficiency ; Liver diseases ; Liver failure ; MISOT ; Mesenchymal stem cells ; Stem cells ; Tolerance
[en] BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS: Ten liver transplant recipients under standard immunosuppression received 1.5-3x106/kg third-party unrelated MSCs on post-operative day 3+/-2, and were prospectively compared to a control group of 10 liver transplant recipients. As primary end-points, MSC infusional toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary end-points, 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. RESULTS: 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 end-points, 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. CONCLUSIONS: 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. LAY SUMMARY: Therapy with mesenchymal stromal cells (MSCs) has been proposed as a mean 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 10 liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression.
http://hdl.handle.net/2268/209463
10.1016/j.jhep.2017.03.001
Copyright (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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