Amniotic Mesenchymal Tissue Cells Inhibit Dendritic Cell Differentiation of Peripheral Blood and Amnion Resident Monocytes

Abstract

Cells derived from the amniotic membranes of human term placenta have drawn much interest for their characteristics of multipotency and low immunogenicity, supporting a variety of possible clinical applications in the field of cell transplantation and regenerative medicine. We have previously shown that cells derived from the mesenchymal region of human amnion (AMTC) can strongly inhibit T-lymphocyte proliferation. In this study, we demonstrate that AMTC can block differentiation and maturation of monocytes into dendritic cells (DC), preventing the expression of the DC marker CD1a and reducing the expression of HLA-DR, CD80, and CD83. The monocyte maturation block resulted in impaired allostimulatory ability of these cells on allogeneic T cells. In attempting to define the mechanisms responsible for these findings, we have observed that the presence of AMTC in differentiating DC cultures results in the arrest of the cells to the G 0 phase and abolishes the production of inflammatory cytokines such as TNF-α, CXCL10, CXCL9, and CCL5. Finally, we also demonstrate that the monocytic cells present in the amniotic mesenchymal region fail to differentiate toward the DC lineage. Taken together, our data suggest that the mechanisms by which AMTC exert immumodulatory effects do not only relate directly to T cells, but also include inhibition of the generation and maturation of antigen-presenting cells. In this context, AMTC represent a very attractive source of multipotent allogeneic cells that promise to be remarkably valuable for cell transplantation approaches, not only due to their low immunogenicity, but also because of the added potential of modulating immune responses, which could be fundamental both for controlling graft rejection after transplantation and also for controlling diseases characterized by inflammatory processes.

Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?

“…Human-and mousederived av-MSCs improved bleomycin-induced lung fibrosis in a mouse model [36]. In vitro, av-MSCs suppressed Tlymphocyte proliferation [37,38], and prevented differentiation of monocytes into dendritic cells [39].…”

“…av-MSCs are also known to secrete a variety of immunomodulatory factors [13,37,[39][40][41][42]. The application of Cdm from av-MSCs reduced progression of lung fibrosis in a mouse model [43] and led to favorable clinical outcomes when treating tendon and ligament injuries in horses [44].…”

Dehydrated human amnion/chorion membrane regulates stem cell activity in vitro

“…Recently, multipotent MSCs have also been isolated in placental tissues, including the amnion and chorion layers of the amniotic membrane,21, 22, 23, 24 and these amniotic membrane derived stem cells have demonstrated the ability to regulate immune cells though secretion of various immunomodulatory cytokines 25, 26, 27, 28…”

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“…Little information is available about the effector molecules from human amniotic mesenchymal stromal cells responsible for this suppression, but these molecules may include prostaglandin E2, tumor necrosis factor γ, interleukin 10, transforming growth factor β, and soluble human leukocyte antigen G. [34][35] Studies with 1-way lymphocyte reactions have shown that human amniotic mesenchymal stromal cells do not induce human T-cell proliferation. 32 In the present study, we showed that human amniotic mesenchymal stromal cells may induce inhibitory effects on allogeneic and xenogeneic T cells in 2-way mixed lymphocyte reactions.…”

“…[29][30][31] In addition, human amniotic mesenchymal stromal cells may modulate immune cell activities and may be transplanted across major histocompatibility complex barriers. [32][33] Amniotic cells may suppress T-cell proliferation because of cell-cell contact and secrete of cytokines. Little information is available about the effector molecules from human amniotic mesenchymal stromal cells responsible for this suppression, but these molecules may include prostaglandin E2, tumor necrosis factor γ, interleukin 10, transforming growth factor β, and soluble human leukocyte antigen G. [34][35] Studies with 1-way lymphocyte reactions have shown that human amniotic mesenchymal stromal cells do not induce human T-cell proliferation.…”