Immunoregulatory impact of human mesenchymalconditioned media and mesenchymal derived exosomes on monocytes

Mesenchymal stem cells (MSCs) are well known due to their immunomodulatory effect, but the exact mechanisms have not been defined. Several studies demonstrated that the exerted immunoregulatory effect of these cells could be mediated by paracrine factors to illustrate, cytokines, chemokine, and among which, extracellular vesicles are one of them to play a crucial role. Moreover, it is assumed that extracellular vesicles are an essential player in intracellular communication by transferring their component. In this respect, the efficiency of conditioned media and exosomes was compared to illustrate a practical approach to cellfree based therapies. In the current study, we investigated the effect of both MSCs conditioned media (MSCCM) and MSCsderived exosomes on the expression of proinflammatory and antiinflammatory cytokines in peripheral blood mononuclear cells (PBMCs). In this regard, isolated PBMCs were treated with MSCCM and MSCderived exosome as separated groups. Expression of inflammatory and antiinflammatory markers was evaluated by Realtime PCR and ELISA. The immunoregulatory effect of MSCCM on proinflammatory and antiinflammatory genes, such as IL12b, iNOS, EGR2, IL10 with an exception in case of IL6 was more significant. Whereas in protein levels IL10 showed the most substantial difference in exosome treated groups. It could be assumed that MSCCM has more immunoregulatory impact on monocyte in contrast with exosomes.Taken together, by considering the recent approaches to cellfree therapy and the immunoregulatory impact of MSCs, yet relatively little is known about the efficacy of humanMSCCM and secreted exosome compared with each other.