Chapter 5 Immunoregulatory Functions of Mesenchymal Stromal Cells

摘要

In vitro and in vivo studies have demonstrated that mesenchymal stem cells (MSCs) are not immunogenic and do not have immunomodulatory effects. MSCs do not express class II antigens, FAS ligand, or co-stimulator molecules (CD80, CD86, CD40, CD40L). They have low expression of primary human leukocyte antigens (HLA-I). In vitro, MSCs in bone, cartilage, muscle, or fat differentiate in the case of HLA-I expression but do not express HLA-II antigens. However, the immunogenic effects of in vivo differentiated MSCs are controversial. MSCs suppress naive T lymphocytes, memory T lymphocytes, effector T lymphocytes, B lymphocytes, and natural killer (NK) cell functions. They are ineffective against the natural immune response of T lymphocytes. In the presence of antigen-presenting cells or antibodies, the addition of MSCs to a culture medium that includes HLA mismatch lymphocytes prevents T-lymphocyte stimulation. MSCs increase with B-lymphocyte viability in vitro and suppress interleukin-2 (IL-2)-related NK cell proliferation and the effector functions of NK cells. MSCs partially reduce the expression of major histocompatibility complex II and CD40 and CD86 co-stimulatory molecules from mature dendritic cells (DCs) by secreting a high rate of IL-6 and vascular endothelial growth factor and thus suppress DC-mediated T-lymphocyte proliferation.