ABSTRACT
Objective To study the immunogenicity,immune modulatory effects and mechanisms of mesenthymal stem ceils (MSCs) derived from the bone marrow of patients with multiple myeloma (MM).Methods The mononuclear cells from the bone marrow of MM patients were obtained and cultured.Immunophenotypes were investigated by using FACS.The levels of cytokines were determined by using enzyme linked immunosorbant assay (ELISA).The endocytosis of monocyte-derived dendritic cells (DCs) was investigated by using FACS.Moreover,the immunoregulatory ability of DCs on proliferation of T lymphocytes was detected by using mixed lymphocyte culture assay.Results MM-derived MSCs had no expression of HLA-DR and costirnulatory molecules (CD40,CD80,CD83 and CD86).MM-derived MSCs could significantly suppress proliferation of T lymphocytes in a dose-dependent manner,which could be reversed by antiTGF-β1 and anti-HGF antibodies.MM-derived MSCs inhibit the endocytosis of DCs.MM-derived MSCs could inhibit the secretion of IL-12 and significantly inhibit the function of DCs on proliferation of T lymphocytes.Conclusion MM-derived MSCs harbored low immunogenicity and immunoregulatory effect in vitro,and this effect was achieved through cytokines.
ABSTRACT
Objective To study the effects and mechanisms of mesenthymal stem cells (MSCs)derived bone marrow of patients with chronic myelogenous leukemia (CML) on function of monocytederived dendritic cells in vitro. Methods Bone marrow mononuclear cells from CML patients were obtained and cultured. Peripheral blood mononuclear cells (PBMCs) derived from normal volunteers were isolated and cultured in DC differentiational condition. Moreover, PBMCs were co-cultured with CML bone marrow-derived MSCs (CML-MSC) or normal volunteers' bone marrow-derived MSC (normal-MSC) in DC differentiational condition. Immunophenotype and the endocytosis of monocytederived DCs were investigated by FACS. The level of IL-12 was evaluated by enzyme linked immunosorbant assay (ELISA). The immunoregulatory ability was detected by mixed lymphocyte culture assay. Results CML-MSCs or normal-MSC inhibited the up-regulation of CD1a,CD40,CD80,CD86,and HLA-DR during DC differentiation and reduced CD40,CD86,and CD83 expression during DC maturation. CML-MSCs inhibited the endocytosis of DCs and decreased their capacity to secret IL-12. CML-MSC could significantly suppress the function of DCs stimulating proliferation of T lymphocytes. Conclusion CML-derived MSCs harbored effect on the differentiation and maturation of DCs in vitro ; CML-MSC could inhibit the immunregulation of DCs.