The successful isolation and culture of human embryonic stem cells (hESCs), being capable of unlimited self-renewal and differentiation into all cell lineages of the body,10 opened a new avenue for MSC derivation. showed that H9-MSCs and BMSCs experienced comparable immunoprivileged properties without triggering allogeneic lymphocyte proliferation as well (S,R,S)-AHPC hydrochloride as comparative immunosuppressive effects on T-cell proliferation induced by either cellular or mitogenic stimuli. Circulation cytometry analysis revealed a lower expression of human major histocompatability complex class II molecule human lymphocyte antigen (HLA)-DR and a higher expression of coinhibitory molecule B7-H1 in H9-MSCs than (S,R,S)-AHPC hydrochloride in BMSCs. Interferon gamma (IFN-) is usually a proinflammatory cytokine that can induce the expression of HLA class II molecules in many cell types. Our results showed that pretreatment of H9-MSCs and BMSCs with IFN- did not switch their immunogenicity and immunosuppressive abilities, but increased the difference between H9-MSCs and BMSCs for their expression of HLA-DR. Further detection of expression of molecules involved in IFN- signaling pathways suggested that the lower expression of HLA-DR in H9-MSCs could be partially attributed to the lower expression and the less nuclear translocation of its transcriptional factor CIITA. The present study provides evidence that this hESC-derived MSCs share comparable immunogenicity and immunosuppressive abilities with BMSCs, but differ in the expression profile of immunological markers and the responsiveness to certain inflammatory cytokines, which suggests that H9-MSCs could be a safe and efficient candidate for MSC treatment in patients with inflammatory disorders. Introduction Mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitors present in (S,R,S)-AHPC hydrochloride the stromal portion of adult and fetal tissues, in particular, from your bone marrow and adipose. 1C4 Apart from their Rabbit polyclonal to TIE1 multilineage differentiation potentials, the immunoprivileged and immunomodulatory properties of MSCs have led them to be attractive candidates for cell therapy and regenerative medicine.5,6 Nevertheless, loss of potency, inconsistent quality, and invasive procedure involved in cell isolation severely limit the use of MSCs in clinical applications.7C9 Therefore, the derivation of MSCs from other consistent sources has been considered as an alternative. The successful isolation and culture of human embryonic stem cells (hESCs), being capable of unlimited self-renewal and differentiation into all cell lineages of the body,10 opened a new avenue for MSC derivation. You will find well-established methods for the differentiation of hESCs into functional MSCs with immunomodulatory properties.11C15 However, the differences between hESC-derived MSCs and tissue-derived MSCs in their immunological characteristics and the underlying mechanisms have not been well defined as yet. The immunoprivileged status of MSCs was partly due to the lack of expression of major histocompatibility complex class II (MHC-II) and costimulatory molecules.16 The MHC-II antigen is constitutively expressed on professional antigen-presenting cells (APC). It binds peptide fragments derived from pathogens and displays them around the cell surface for acknowledgement by the appropriate T cells.16,17 The best-studied costimulatory molecules belong to the B7 family, which consists of seven known users: CD80 (B7.1), CD86 (B7.2), B7-H1 (programmed death-1 ligand [PD-L1]), B7-H2 (inducible costimulator ligand), B7-DC (programmed death-2 ligand [PD-L2]), B7-H3, and B7-H4. They bind to receptors on lymphocytes and regulate immune responses by directing either costimulatory or coinhibitory signals.18 Interferon gamma (IFN-), a major proinflammatory cytokine secreted by activated T cells and natural killer (NK) cells,19 can markedly stimulate or increase the expression of MHC-II molecules in many cell types and control the APC function of MSCs by regulating the expression of class II transactivator (CIITA), the grasp regulator of MHC-II.16,19C21 However, the influence of IFN- around the immunogenicity of MSCs is still surrounded by controversy.22C26 The immunomodulatory properties of MSCs have been extensively studied both and studies have demonstrated that MSCs could promote engraftment of CD34+ hematopoietic stem cells,32 reduce incidence of graft-versus-host diseases in patients receiving allogenic transplants,33 ameliorate autoimmune diseases,34,35 and prevent the rejection of allogeneic skin grafts.36 Direct cell contact with immune cells37 and soluble factors produced by MSCS, such as IL-6,38 TGF-,39,40 hepatocyte growth factor,41 nitric oxide,42 indoleamine 2,3-dioxygenase,43,44 and prostaglandin E2,45,46 have been implicated in the mechanisms of MSC-mediated immunosuppression. In this study, we differentiated H9 hESCs into MSC-like cells (H9-MSCs) through an embryoid body (EB) outgrowth method. The immunological characteristics of H9-MSCs were characterized and compared to bone marrow-derived MSCs (BMSCs) with or without IFN- treatment. Moreover, the expression of genes encoding components in IFN- signaling pathways in H9-MSCs and BMSCs was investigated after IFN- treatment. Our data may provide additional insights into the responsiveness of H9-MSCs and BMSCs under inflammatory conditions after transplantation. Materials and.