Leukemic Relapse Following MMSC Rescue in a Murine Model of GVHD

Abstract

Recently, the use of mesenchymal stem cells (MMSC) for the amelioration of acute graft versus host disease (GVHD) has shown promise as a therapeutic intervention. Given that MSC can suppress allogeneic immune responses, there is a concern that the use of these cells may promote leukemic relapse. Here we present a murine model of GVHD in the presence of leukemic cells (L1210). Acute GVHD was induced with or without prior injection of L1210 leukemia cells. The mice were treated with primary MMSC or a mesenchymal cell line (OMA‐AD). The results without L1210 cells, demonstrated that mice treated with primary MMSC had developed moderate GVHD but had increased long‐term survival when compared to controls. The group treated with OMA‐AD cells demonstrated a protective effect against GVHD, and the survival rate was superior to that of animals treated with primary MMSC. However, with L1210 present, the control mice lived outlived the OMA‐AD group. Only the mice receiving primary MMSC survived long term. It appears that although MMSC and OMA‐AD cells can both ameliorate GVHD, the greater immunosuppressive effect of OMA‐AD cells permitted the growth of the leukemic cells. The moderate GVHD that remained after MMSC treatment eliminated the leukemia in the majority of mice. These studies demonstrated that in mice, administration of MMSC can ameliorate GVHD but the complete suppression of GVHD appears to permit leukemic relapse.