Oct4-negative multipotent adult progenitor cells and mesenchymal stem cells as regulators of T-cell alloreactivity in mice

Abstract

Multipotent adult progenitor cells (MAPC) are clinically being explored as an alternative to mesenchymal stem cells (MSC) for the immunomodulatory control of graft-versus-host disease (GvHD). Here, we performed an explorative study of the immunomodulatory potential of mouse MAPC (mMAPC), in comparison with that of MSC (mMSC) using experimental models of T-cell alloreactivity. Suppressive effects of Oct4-expressing mMAPC have been described previously; here, we studied mMAPC expressing low to no Oct4 ('mClone-3'), recently shown to be most representative for the human MAPC counterpart. mClone-3 and mMSC exhibited similar immunophenotype and in vitro immunogenic behavior. Allogeneic T-cell↔dendritic cell-proliferation assays showed strong dose-dependent T-cell-suppressive effects of both mClone-3 and mMSC. In a popliteal lymph node assay, mClone-3 and mMSC equally suppressed in vivo alloreactive T-cell expansion. We conclude that mouse MAPC and MSC exhibit similar immunosuppressive behavior in in vitro and local in vivo GvHD assays.