Human mesenchymal stem cells (hMSCs) are well-known for their immunomodulatory potential. In recent clinical trials and in vivo studies, hMSCs were used as therapeutic measures to dampen inflammation. In this context, their effect on macrophages in vivo has been described to induce a phenotype change shifting from a proinflammatory to an anti-inflammatory environment. Despite several in vitro studies that investigated the potential of hMSCs to inhibit the polarization of macrophages into the proinflammatory M1 subtype, it is still unclear if hMSCs affect polarized M1 macrophages or if they control the environment by inhibiting the M1 polarization of unpolarized macrophages. Here, a comparative in vitro investigation of hMSC immunomodulation via soluble factors concerning the influence on the polarization of macrophages to M1 and on polarized M1 macrophages is presented. Human primary monocyte-derived macrophages (hMDMs) as well as THP-1 cells were used for this investigation. The macrophage subtype was analyzed by gene expression as well as cytokine secretion. hMSCs affected cytokine secretion of polarizing macrophages, while changes in gene expression were evident in polarized M1 macrophages. These effects were observed in THP-1 and hMDM macrophages. In conclusion, we suggest that hMSCs implement their immunomodulatory effects on polarizing and polarized macrophages in different ways.

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