Mesenchymal Stromal Cells (MSCs) are non-hematopoietic stromal cells which have been used in the clinic during the last decades to treat a number of inflammatory diseases due to their immunomodulatory properties. However, little is known about the mechanism of interaction of MSCs with the immune system, partly since they appear to be lacking in the circulation in the circulation shortly after their infusion. Recent studies using bone marrow or umbilical cord derived MSCs showed that monocytes are capable of engulfing MSCs suggesting that their immunomodulatory response can be mediated through these cells.

Here, we generated and expanded MSCs from the placental decidua basalis tissue and studied their interactions with human monocytes. Using both live cell imaging and flow cytometry, we demonstrated that CD14⁺ monocytes engulf both dead and live MSCs. Phagocytosis induced a positive effect on monocyte survival and stabilization of receptor expressions at their surface. Classical monocytes (CD14⁺CD16^-) which engulfed MSCs switched into intermediate monocytes (CD14⁺CD16⁺). Subsequently, intermediate monocytes upregulated the expression of the two M2 immunosuppressive markers CD163 and CD206. Surprisingly, cells present in PBMC preparations inhibited this process. Instead, monocytes then displayed an M1 phenotype with upregulation of the co-stimulatory marker CD86. Together, during my thesis, I have successfully generated MSCs from the placenta and performed a comprehensive analysis of their interactions with human monocytes using different techniques.