Abstract
BackgroundLiver transplantation is the definitive treatment for many end-stage liver diseases. However, the life-long immunosuppression needed to prevent graft rejection causes clinically significant side effects. Cellular immunomodulatory therapies may allow the dose of immunosuppressive drugs to be reduced. In the current protocol, we propose to complement immunosuppressive pharmacotherapy with third-party multipotent adult progenitor cells (MAPCs), a culture-selected population of adult adherent stem cells derived from bone marrow that has been shown to display potent immunomodulatory and regenerative properties. In animal models, MAPCs reduce the need for pharmacological immunosuppression after experimental solid organ transplantation and regenerate damaged organs.MethodsPatients enrolled in this phase I, single-arm, single-center safety and feasibility study (n = 3-24) will receive 2 doses of third-party MAPCs after liver transplantation, on days 1 and 3, in addition to a calcineurin-inhibitor-free "bottom-up" immunosuppressive regimen with basiliximab, mycophenolic acid, and steroids. The study objective is to evaluate the safety and clinical feasibility of MAPC administration in this patient cohort. The primary endpoint of the study is safety, assessed by standardized dose-limiting toxicity events. One secondary endpoint is the time until first biopsy-proven acute rejection, in order to collect first evidence of efficacy. Dose escalation (150, 300, 450, and 600 million MAPCs) will be done according to a 3 + 3 classical escalation design (4 groups of 3-6 patients each).DiscussionIf MAPCs are safe for patients undergoing liver transplantation in this study, a phase II/III trial will be conducted to assess their clinical efficacy.
Highlights
Liver transplantation is the definitive treatment for many end-stage liver diseases
The primary objective of this study is to assess the safety of multipotent adult progenitor cells (MAPCs) infusions in patients undergoing liver transplantation
Immunomonitoring will be performed on blood samples from all participating patients to assess the anti-donor immune response, the composition of circulating T cell subpopulations, the anti-donor antibody response and to identify a putative biomarker signature that is associated with transplant tolerance
Summary
Liver transplantation is the definitive treatment for many end-stage liver diseases. the lifelong immunosuppression needed to prevent graft rejection causes clinically significant side effects. Growing numbers of patients in need of a liver graft are faced with a continuous shortage of donor organs. In the Eurotransplant area, for instance, only 1631 transplant livers were available for 2641 patients on the waiting list in 2009 [12]. To overcome this shortage, criteria for the acceptance of donors have been liberalized, e.g., in terms of prolonged ischemia time, increased donor age, or the presence of clinically significant donor liver steatosis. We propose a novel protocol involving treatment of liver transplant recipients with multipotent adult progenitor cells (MAPCs) with the goal of reducing the dose of immunosuppressive drugs and of supporting liver regeneration in marginal grafts
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
