Open Access Protocol

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

Felix C Popp1, Barbara Fillenberg1, Elke Eggenhofer1, Philipp Renner1, Johannes Dillmann1, Volker Benseler1, Andreas A Schnitzbauer1, James Hutchinson1, Robert Deans2, Deborah Ladenheim2, Cheryl A Graveen2, Florian Zeman3, Michael Koller3, Martin J Hoogduijn4, Edward K Geissler1, Hans J Schlitt1 and Marc H Dahlke1*

Author Affiliations

1 Department of Surgery, University Medical Center Regensburg, Regensburg, Germany

2 Athersys Inc., Cleveland, Ohio, USA

3 Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany

4 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Journal of Translational Medicine 2011, 9:124  doi:10.1186/1479-5876-9-124

Published: 28 July 2011

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.