Heart Grafts Tolerized Through Third-Party Multipotent Adult Progenitor Cells Can Be Retransplanted to Secondary Hosts With No Immunosuppression

E Eggenhofer, FC Popp, M Mendicino, P Silber, W van't Hof, P Renner, Martin Hoogduijn, J Pinxteren, N van Rooijen, EK Geissler, R Deans, HJ Schlitt, MH Dahlke

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35 Citations (Scopus)

Abstract

Multipotent adult progenitor cells (MAPCs) are an adherent stem cell population that belongs to the mesenchymal-type progenitor cell family. Although MAPCs are emerging as candidate agents for immunomodulation after solid organ transplantation, their value requires further validation in a clinically relevant cell therapy model using an organ donor- and organ recipient-independent, third-party cell product. We report that stable allograft survival can be achieved following third-party MAPC infusion in a rat model of fully allogeneic, heterotopic heart transplantation. Furthermore, long-term accepted heart grafts recovered from MAPC-treated animals can be successfully retransplanted to naive animals without additional immunosuppression. This prolongation of MAPC-mediated allograft acceptance depends upon a myeloid cell population since depletion of macrophages by clodronate abrogates the tolerogenic MAPC effect. We also show that MAPC-mediated allograft acceptance differs mechanistically from drug-induced tolerance regarding marker gene expression, T regulatory cell induction, retransplantability, and macrophage dependence. MAPC-based immunomodulation represents a promising pathway for clinical immunotherapy that has led us to initiate a phase I clinical trial for testing safety and feasibility of third-party MAPC therapy after liver transplantation.
Original languageUndefined/Unknown
Pages (from-to)595-606
Number of pages12
JournalStem cells translational medicine
Volume2
Issue number8
DOIs
Publication statusPublished - 2013

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