Compared with other stem cell sources, such as hematopoietic stem cells (HSCs), MSCs appear as a promising source for overcoming autoimmunity because of their immunosuppressive properties [
20]. MSCs modulate the immunological activity of different cell populations as shown by in vitro data. Their most important effects are T-cell proliferation and dendritic cell (DC) differentiation inhibition, which are key activating factors of autoimmune disorders. MSCs are effective in inhibiting proliferation of CD4 and CD8 T cells as well as memory and naïve T cells [
21]. This mechanism relies on both cell–cell contact and several specific mediators, produced by MSCs, such as TGF-β1, prostaglandin E
2, and indoleamine 2,3 deoxygenase [
22]. The ability to suppress T-cell responses to mitogenic and antigenic signals is explained by a complex mechanism of induction of “division arrest anergy”, responsible for maintaining T lymphocytes in a quiescent state. Thus, the MSCs trigger the inhibition of cyclin D2 expression, thus arresting cells in the G
0/G
1 phase of the cell cycle [
23]. MSCs also inhibit the production of interferon-gamma (IFN-γ) and increase the production of IL-4 by T helper 2 cells. This indicates a shift in T cells from a pro-inflammatory state to an anti-inflammatory state [
24,
25]. MSCs also stimulate the production of CD4
+CD25
+ regulatory T cells, which inhibit lymphocyte proliferation in allogeneic transplantation [
26]. In addition, MSCs inhibit B-cell proliferation through arrest at the G
0/G
1 phase of the cell cycle and production of IgM, IgA, and IgG as well as their chemotactic abilities [
27,
28]. A recent study demonstrated that this effect of MSCs on B cells is mediated by T cells [
29]. However, some contradictory data showed that, in some culture conditions, IgG secretion and B-cell proliferation can be induced and B-cell survival sustained, and this effect does not depend on the presence of IFN-γ in the culture [
30,
31]. MSCs have been demonstrated to interfere with DC differentiation, maturation, and function [
32‐
34]. MSCs obtained from healthy human donors can indirectly reduce T-cell activation by inhibiting DC differentiation (mainly DC type I) from monocytes [
35].
Although the majority of data dealing with the immunomodulatory effects of MSCs are derived from BM-MSCs, some of these effects have also been described for MSCs from other sources. Results from studies comparing the immunomodulatory effects of various tissue-derived MSCs are controversial. Some studies concluded that BM- and UC-MSCs show similar effects, whereas others demonstrated that UC-MSCs have a higher capacity of inhibiting T-cell proliferation than adult MSCs [
36,
37]. Some studies also indicate that AT-MSCs can be more effective suppressors of immune response compared with BM-MSCs. Indeed, AT-MSCs modulate mitogen-stimulated B-cell immunoglobulin production in vitro to a much greater extent than BM-MSCs. Also, in comparison with BM-MSCs, they inhibit, significantly more, the differentiation of blood monocytes into DCs and the expression of functionally important co-stimulatory molecules on the surface of mature monocyte-derived DCs [
38,
39]. It may be postulated that MSCs express a different set of molecules depending of their tissue of origin, resulting in different immunosuppressive activities. Taken together, these in vitro data demonstrate that MSCs modulate the action of the various cells that are involved in immune response and preferentially inhibit T-cell proliferation and differentiation of DCs. However, it would be important to further investigate the molecular mechanisms that underlie the immunomodulatory properties of various tissue-derived MSCs since these differences may have functional relevance to the therapeutic use of these cells.