Comparative Study of Immune Regulatory Properties of Stem Cells Derived from Different Tissues.

Allogeneic stem cell-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some stem cell (SC) types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow-MSCs, olfactory ecto-mesenchymal stem cells, leptomeningeal stem cells, and three different c-Kit-positive SC types, i.e. amniotic fluid SCs, cardiac SCs, and lung SCs. We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers ICAM-1, VCAM-1, HLA-ABC and HLA-DR, modulatory activity towards purified T, B and NK cells, lower immunogenicity of inflammatory-primed SCs as compared to resting SCs, and IDO-activation as molecular inhibitory pathways, with some SC type-related peculiarities. Moreover, the SC types analyzed exert an anti-apoptotic effect towards not-activated immune effector cells. In addition, we found that the inhibitory behavior is not a constitutive property of SCs, but is acquired as a consequence of immune effector cell activation, as previously described for MSCs. Thus, immune regulation is a general property of stem cells and the characterization of this phenomenon may be useful for a proper therapeutic use of SCs.