Immunosupressive properties of human placenta-derived mesenchymal stem cells on control of acute graft-versus-host disease in mice.

Abstract

6547 Background: Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is still associated with significant morbidity and mortality. High-dose corticosteroids are standard in initial treatment of patients with acute GVHD achieving response rates of 30-70%. However, no standard therapy exists once a patient has developed acute GVHD refractory to corticosteroids. In this respect, the immunomodulatory properties of mesenchymal stem cells (MSC) have been applied to reduce the incidence the GVHD after allogeneic HSCT. Among the various sauces of MSC which have immunomodulatory effect in vitro, only human placenta MSC (hP-MSC) has not elucidated in the GVHD in vivo model. In this study, we characterize the phenotype of hP-MSC, investigate their immunomodualotory properties in vitro and evaluate the clinical possibilities of hP-MSC for the control of GVHD in MHC mismatch mice model. Methods: A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. To control the GVHD, hP-MSC was transplanted to recipient mice (5 x 105 or 1 x 106). Results: We purified and expanded the hP-MSC characterized by flow cytometry (positive for CD105, CD73, CD44, CD56 and HLA-ABC but negative for CD3, CD14, CD31, CD45, CD11a, CD34 and CD117). These cells also exhibited mesenchymal differentiation potential, as assessed by culturing in adipogenic, osteogenic, or chondrogenic medium. In vitro experiment, the hP-MSC suppressed mitogen-stimulated T cell proliferation in a dose-dependent manner. Moreover, hP-MSC inhibited cytokine secretion (IL-12, TNF-α, and INF-γ) of T-cells in response to mitogen. In vivo experiment, survival rate in hP-MSC (1x106) group was higher than in the control group, and histological scores were low in hP-MSC (1x106) group. Conclusions: We conclude that hP-MSC can efficiently control the GVHD associated with allogeneic HSCT in mice model.