Embryonale Stammzellen unterdrücken die Graft-versus-Host Reaktion nach allogener Knochenmarktransplantation im Rattenmodell

Abstract

Successful application of bone marrow or blood stem cells for the treatment of hematological or autoimmune diseases depends on reliable engraftment of the injected cells in allogeneic hosts. Moreover, the frequency of the T cell population transferred with the graft determines the risk of serious graft-versus-host reactions in myeloablated or otherwise conditioned hosts. Here we show that the use of embryonic stem-cell-derived suppressor cells (SC-C12) of WKY-origin [RTL.¹] support the engraftment of non-T cell depleted allogeneic bone marrow cells of DA origin [RTl.^avl] in LEW recipients [RTl.¹] while, simultaneously, T cell-associated graft-versus-host reactions are suppressed. Noteworthy, combined injections of donor (DA)-derived bone marrow cells (l×l0⁸) together with l×l0⁶ MHC-mismatched SC-12 (WKY) cells resulted in donor (DA) chimerism (>95% donor cells) or mixed chimerism (15–35% donor cells) in myeloablated and non-myeloablated LEW host rats, respectively. These findings open a new field for the use of embryonic-derived suppressor cells as „bystander cells“ for stable engraftment of MHC-unrelated bone marrow stem cells in the field of allogeneic bone marrow transplantation.