Table 2.

Immunomodulatory properties of MSCs. The table summarises the diverse mechanisms by which MSCs perform their immunomodulatory functions via cell–cell contact or paracrine effects. Dendritic cells (DCs); interferon gamma (IFNγ);indoleamine 2,3-dioxygenase (IDO); interleukin (IL); hepatocyte growth factor (HGF); leukaemia inhibitory factor (LIF); natural killer cells (NK); nitric oxide (NO); prostaglandin-E2 (PGE2); soluble human leukocyte antigen G (sHLA-G); transforming growth factor-beta (TGFβ); tumour necrosis factor-alpha (TNFα); regulatory T-cells (Treg); vascular endothelial growth factor (VEGF).

Property of MSC	Mechanism
Suppression of T-cell activity	Inhibition of antigen-specific proliferation (both for naive and memory T-cells). IFNγ and IL4 production. Arrest of T-cells in the G0/G1 cell cycle phase.
Inhibition of B-cells	Block of activated B-cell proliferation. Decrease in antibody production. Suppression of B-cell chemotaxis by reducing surface expression of the chemokine receptors on B-cells.
Activation of regulatory T-cells	Increase production of sHLA-G, inducing the differentiation of Treg-cells. Induction of Tregs is caused by cell-to-cell contact with MSCs and by the secretion of PGE2 and TGFβ1.
Inhibition of NK cells	Production of TGFβ, sHLA-G, and PGE2. Cell–cell contact inhibits NK cell cytotoxicity.
Induction of macrophages with anti-inflammatory immunophenotype	PGE2 induction of macrophages to produce IL10. Phagocytosis of dead MSCs by macrophages leads to appearance of alternatively activated macrophages characterised by increased production of IL10, TGFβ3, and IL6, and decreased TNFα and IL12 secretion. MSC-educated macrophages have increased expression of alternatively activated macrophages markers CD206 and CD163 and the inhibitory molecules PD-L1 and PD-L2.
Regulating lymphopoiesis	BM-MSC regulate the development of T- and B-lymphocytes through the action of growth factors, cytokines, and adhesion molecules.
Interaction with DC	MSCs negatively regulate DC differentiation from CD14+ monocytes and CD34+ progenitor cells by altering the expression of the DC surface antigens and IL12 production.
Paracrine effects of MSCs	Secretion of growth factors, anti-inflammatory cytokines, chemokines, (IL10, IL6, TGFβ, VEGF, sHLA-G, HGF, IDO, NO, PGE2, and LIF). Suppression of pro-inflammatory cytokine (IFNγ, IL1β, TNFα) production. Extracellular vesicles contain bioactive molecules, including mRNA and miRNA and mitochondria.