Fig. 3

MSC—Immune cell interactions. Initial studies envisioned autologous use of MSCs. However, studies with immune cells demonstrated that MSCs are not immediately rejected by T cells and other immune cells, prompting the study of allogeneic MSCs in mutiple therapies. MSCs produce at least 11 factors known to affect immune cells. When interacting with T cells (pathways 1 and 5) MSCs cause a reduction in inflammatory T H1 and an increase in T Regs and T H2 cells with the concomitant decrease in IFNγ, increase in IL-10, IL-4 and IL-5. When MSCs interact with dendritic cells (pathways 2, 3,and 4) there is a decrease in proinflammatory mature DC1 with a decrease in TNF-α and IL-12, and an increase in immature DC and DC2, with increased expression of IL-10. When MSCs interact with natural killer cells (pathway 6) there is a decrease in the expression of IFNγ. When macrophages interact with MSCs (pathway 7), there is a decrease in the proinflammatory M1 phenotype and an increase in the anti-inflammatory M2 phenotype, with increased PGE2, TSG-6 and IL-1RA. MSCs can also reduce the secretion of antibodies from B cells (pathway 8) and inhibit bacterial growth by a direct or indirect mechanism (pathway 9). This figure is used with permission from Blood/Aggarwal and Pittenger¹¹⁶ and has been updated/modified from its original form.