Figure 2: Proposed immunomodulatory mechanisms of MSCs in a vascularized composite allotransplantation (VCA). MSCs mediate their immunomodulatory effects by interacting with cells from both the innate (DCs, macrophages, NK cells) and adaptive immune (T cells and B cells) systems, particularly through the regulation of T-cell proliferation and the inhibition of DC differentiation. MSC inhibition of TNF-   and IFN-γ secretion, promotion of IL-10 and TGF-β secretion, and IDO and PGE2 expression may affect the maturation states and functional properties of DCs, resulting in skewing of the immune response toward the prolongation of VCA survival. DC: dendritic cells; IFN-γ: interferon (IFN)-γ; IDO: indoleamine-2,3-dioxygenase; NK: natural killer; PGE2: prostaglandin E2; : regulatory T-cells; TGF-β: transforming growth factor-β; TNF- : tumor necrosis factor (TNF)- .