title: Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting.
abstract: Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic value in allogeneic transplantation to prevent graft rejection and to prevent and treat graft-versus-host disease. In the present study, we examined the in vivo immunomodulatory properties of MSCs in murine models of allogeneic bone marrow (BM) transplantation. Sublethally irradiated recipients received allogeneic BM with or without host or donor MSCs. The addition of host MSCs significantly enhanced the long-term engraftment associated with tolerance to host and donor antigens. However, the infusion of donor MSCs was associated with significantly increased rejection of allogeneic donor BM cells. Moreover, we showed that the injection of merely allogeneic donor MSCs in naive mice was sufficient to induce a memory T-cell response. Although the observed engraftment-promoting effects of host MSCs in vivo support the therapeutic potential of MSCs, our results also indicate that allogeneic MSCs are not intrinsically immunoprivileged and that under appropriate conditions, allogeneic MSCs induce a memory T-cell response resulting in rejection of an allogeneic stem cell graft.
authors.affiliation: Laboratory of Experimental Hematology, Department of Hematology, D2-P, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. nauta@lumc.nl
authors.forename: Alma J
authors.initials: AJ
authors.lastname: Nauta
authors.forename: Geert
authors.initials: G
authors.lastname: Westerhuis
authors.forename: Alwine B
authors.initials: AB
authors.lastname: Kruisselbrink
authors.forename: Ellie G A
authors.initials: EG
authors.lastname: Lurvink
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D049109:Cell Proliferation; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D007108:Immune Tolerance; D007156:Immunologic Memory; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic