Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study

JOURNAL OF HEPATOLOGY

卷:67

Article

Detry, Olivier^1,2  Vandermeulen, Morgan^1,2  Delbouille, Marie-Helene¹  Somja, Joan³  Bletard, Noella³  Briquet, Alexandra⁴  Lechanteur, Chantal⁴  Giet, Olivier⁴  Baudoux, Etienne⁴  Hannon, Muriel⁵  Baron, Frederic^5,6  Beguin, Yves^5,6 

[1] Univ Liege, CHU Liege, Dept Abdominal Surg & Transplantat, CHU ULg, Liege, Belgium

[2] Mesenchymal Stromal Cell Solid Organ Transplantat, Liege, Belgium

[3] Univ Liege, CHU Liege, Dept Pathol, CHU ULg, Liege, Belgium

[4] Univ Liege, CHU Liege, LTCG, CHU ULg, Liege, Belgium

[5] Univ Liege, Interdisciplinary Cluster Appl Genoprote GIGA Hae, Liege, Belgium

[6] Univ Liege, CHU Liege, Dept Haematol, CHU ULg, Liege, Belgium

关键词: Stem cells;    Mesenchymal stem cells;    Cell therapy;    Liver failure;    Liver diseases;    Hepatic insufficiency;    Cirrhosis;    Immune tolerance;    Cancer;    MISOT;   

DOI  :  10.1016/j.jhep.2017.03.001

来源: Elsevier

【 摘 要 】

Background & Aims: 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. Methods: Ten liver transplant recipients under standard immunosuppression received 1.5-3 x 10(6)/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. 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 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. 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 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. Clinical trial registration number: Eudract: # 2011-001822-81, ClinicalTrials.gov: # NCT 01429038. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V.

【 授权许可】

Free