title: Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I).
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Felix C
authors.initials: FC
authors.lastname: Popp
authors.forename: Barbara
authors.initials: B
authors.lastname: Fillenberg
authors.forename: Elke
authors.initials: E
authors.lastname: Eggenhofer
authors.forename: Philipp
authors.initials: P
authors.lastname: Renner
authors.forename: Johannes
authors.initials: J
authors.lastname: Dillmann
authors.forename: Volker
authors.initials: V
authors.lastname: Benseler
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.forename: James
authors.initials: J
authors.lastname: Hutchinson
authors.forename: Robert
authors.initials: R
authors.lastname: Deans
authors.forename: Deborah
authors.initials: D
authors.lastname: Ladenheim
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Graveen
authors.forename: Florian
authors.initials: F
authors.lastname: Zeman
authors.forename: Michael
authors.initials: M
authors.lastname: Koller
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Marc H
authors.initials: MH
authors.lastname: Dahlke
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000637:transplantation*; D026661:Clinical Trials Data Monitoring Committees; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation; D039902:Multipotent Stem Cells / Q000637:transplantation*; D018570:Risk Assessment; D033581:Stem Cell Transplantation / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents