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

Protocol

Cheryl A Graveen¹  Robert Deans¹  Deborah Ladenheim¹  Florian Zeman²  Michael Koller²  Martin J Hoogduijn³  Felix C Popp⁴  Andreas A Schnitzbauer⁴  Elke Eggenhofer⁴  James Hutchinson⁴  Hans J Schlitt⁴  Philipp Renner⁴  Volker Benseler⁴  Marc H Dahlke⁴  Johannes Dillmann⁴  Barbara Fillenberg⁴  Edward K Geissler⁴ 

[1] Athersys Inc, Cleveland, Ohio, USA;Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany;Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands;Department of Surgery, University Medical Center Regensburg, Regensburg, Germany;

关键词: Acute Rejection;    Liver Transplant Recipient;    Basiliximab;    Mycophenolic Acid;    Acute Rejection Episode;   

DOI  :  10.1186/1479-5876-9-124

 received in 2011-05-10, accepted in 2011-07-28,  发布年份 2011

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Popp et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.