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Heart grafts tolerized through third-party multipotent adult progenitor cells can be retransplanted to secondary hosts with no Immunosuppression

By E. (Elke) Eggenhofer, F. (Felix) Popp, A. (Angela) Mendicino, P. (Paula) Silber, W. (Wouter) Van'T Hof, P. (Philipp) Renner, M.J. (Martin) Hoogduijn, J. (Jef) Pinxteren, N. (Nico) van Rooijen, E.K. (Edward) Geissler, R. (Robert) Deans, H.J. (Hans) Schlitt and M.H. (Marc) Dahlke

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, thirdparty 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 naïve 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

Topics: Immunosuppression, Mesenchymal stem cells, T cells, Transplantation
Year: 2013
DOI identifier: 10.5966/sctm.2012-0166
OAI identifier: oai:repub.eur.nl:75193
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