Poster (Scientific congresses and symposiums)
Infusion of third-party mesenchymal stromal cells after liver transplantation: a phase 1, open-label, clinical study
DETRY, Olivier; VANDERMEULEN, Morgan; DELBOUILLE, Marie-Hélène et al.
201522nd Annual Meeting
 

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Abstract :
[en] Transplanted patients have to deal with numerous side effects of life-long dependence on immunosuppressive drugs. Paradoxically these drugs fail to prevent acute and/or chronic rejection in many cases. Mesenchymal stromal cells (MSC) are multipotent and self-renewing bone marrow progenitors that have been shown both in vitro and in vivo as capable of (i) immunomodulation, (ii) anti-inflammation in case of ischemia/reperfusion injury, and (ii) stimulation of tissue repair. MSC could therefore be very interesting in organ recipients to limit chronic graft damage and to allow tolerance. This study aimed to be the first clinical evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled, phase I study. Clinical grade MSCs were locally collected from the bone marrow of unrelated healthy donors. They were cultured in a GMP-compliant lab, underwent extensive quality controls and were frozen for storage in a MSC bank. When needed for patient treatment, MSC were thawed and intravenously injected into patients. 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5-3x106/kg MSC on post- operative day 3 ± 2. These patients were prospectively compared to a group of 10 control (MSC-) liver recipients. Primary endpoints were MSC infusion toxicity, and incidence of cancer and opportunistic infections at month 6. Secondary endpoints were patient and graft survivals and rejection at month 6, as well as the effects of MSC on recipients’ immune function and on immunohistology of at month 6 graft biopsies. No MSC infusional toxicity was observed. Both groups were comparable in terms of donor and recipient characteristics. There was no difference in primary end-points between control and MSC groups. No patient developed de novo cancer. There was no statistical difference in patient and graft survivals or in rejection rates. There was no graft rejection in the MSC group. Month-6 graft biopsies were not different according to Banff and fibrosis scores. This phase I study showed excellent tolerability and safety of a single infusion of third-party MSC after liver transplantation. There were no graft safety issues and no excess of immunosuppression after MSC injection. Further analyses of consequences of MSC injection on the immune profile are needed. The possibility of avoiding calcineurin-inhibitors with repeated MSC injections as main immunosuppressive therapy and/of tolerance induction by MSC infusion should be investigated by further studies.
Disciplines :
Hematology
Gastroenterology & hepatology
Surgery
Author, co-author :
DETRY, Olivier  ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdominale- endocrinienne et de transplantation
VANDERMEULEN, Morgan ;  Centre Hospitalier Universitaire de Liège - CHU > Frais communs chirurgie
DELBOUILLE, Marie-Hélène ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdominale- endocrinienne et de transplantation
DE ROOVER, Arnaud ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdominale- endocrinienne et de transplantation
SOMJA, Joan ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
BLETARD, Noëlla ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
BRIQUET, Alexandra ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
LECHANTEUR, Chantal ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
BEGUIN, Yves  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Language :
English
Title :
Infusion of third-party mesenchymal stromal cells after liver transplantation: a phase 1, open-label, clinical study
Publication date :
27 March 2015
Event name :
22nd Annual Meeting
Event organizer :
Belgian Transplantation Society
Event place :
Brussels, Belgium
Event date :
du 27 au 28 mars 2015
Available on ORBi :
since 03 May 2015

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