Article (Scientific journals)
Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
DETRY, Olivier; VANDERMEULEN, Morgan; DELBOUILLE, Marie-Hélène et al.
2017In Journal of Hepatology, 67 (1), p. 47-55
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Keywords :
Cancer; Cell therapy; Cirrhosis; Hepatic insufficiency; Liver diseases; Liver failure; MISOT; Mesenchymal stem cells; Stem cells; Tolerance
Abstract :
[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.
Disciplines :
Hematology
Gastroenterology & hepatology
Surgery
Author, co-author :
DETRY, Olivier  ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdo, sénologique, endocrine et de transplantation
VANDERMEULEN, Morgan ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdo, sénologique, endocrine et de transplantation
DELBOUILLE, Marie-Hélène ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdo, sénologique, endocrine et de transplantation
SOMJA, Joan ;  Centre Hospitalier Universitaire de Liège - CHU > Service dermatopathologie
BLETARD, Noëlla ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques
Briquet, Alexandra ;  Université de Liège > GIGA-R : Hématologie
LECHANTEUR, Chantal ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
GIET, Olivier ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
BAUDOUX, Etienne  ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
Hannon, Muriel ;  Université de Liège > GIGA-R : Hématologie
Baron, Frédéric  ;  Université de Liège > GIGA-R : Hématologie
Beguin, Yves  ;  Université de Liège > GIGA-R : Hématologie
Language :
English
Title :
Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
Publication date :
July 2017
Journal title :
Journal of Hepatology
ISSN :
0168-8278
eISSN :
1600-0641
Publisher :
Elsevier, Netherlands
Volume :
67
Issue :
1
Pages :
47-55
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Available on ORBi :
since 14 April 2017

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