Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I)

Felix C. Popp, Barbara Fillenberg, Elke Eggenhofer, Philipp Renner, Johannes Dillmann, Volker Benseler, Andreas A. Schnitzbauer, James Hutchinson, Robert Deans, Deborah Ladenheim, Cheryl A. Graveen, Florian Zeman, Michael Koller, Martin J. Hoogduijn, Edward K. Geissler, Hans J. Schlitt, Marc H. Dahlke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number124
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
Publication statusPublished - 28 Jul 2011

Bibliographical note

Funding Information:
The development of the study protocol was supported by a restricted grant from Novartis Pharma GmbH, Germany, which was used to fund a position for the study manager (BF). The protocol development was further supported by the Junior Clinical Research Grant of ESOT to MHD.

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