Popp, Felix C. and Fillenberg, Barbara and Eggenhofer, Elke and Renner, Philipp and Dillmann, Johannes and Benseler, Volker and Schnitzbauer, Andreas A. and Hutchinson, James and Deans, Robert and Ladenheim, Deborah and Graveen, Cheryl A and Zeman, Florian and Koller, Michael and Hoogduijn, Martin J and Geissler, Edward K. and Schlitt, Hans J. and Dahlke, Marc H. (2011) Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation - a phase I study (MISOT-I). Journal of translational medicine 9 (1), p. 124.
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BACKGROUND: Liver 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. METHODS: Patients 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). DISCUSSION: If MAPCs are safe for patients undergoing liver transplantation in this study, a phase II/III trial will be conducted to assess their clinical efficacy.
|Institutions:||Medicine > Lehrstuhl für Chirurgie|
|Projects:||Open Access Publizieren (DFG)|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Partially|
|Deposited On:||09 Sep 2011 09:46|
|Last Modified:||20 Mar 2013 13:09|