Revisão bibliográfica : efeito de células estromais mesenquimais viáveis, não-viáveis, apoptóticas e suas partículas subcelulares sobre monócitos e macrófagos

Abstract

Mesenchymal stromal cells (MSCs) present great potential for cell therapy for autoimmune and inflammatory disorders due to its immunoregulatory and regenerative properties. MSCs modulate the inflammatory milieu by releasing soluble factors and acting through cell-to-cell mechanisms, reducing immune cell activation and function and hence inducing immunosuppression. In vitro as well as in vivo MSCs switch the classical inflammatory and M1 status of monocytes and macrophages towards a non-classical and anti-inflammatory M2 phenotype. This is characterized by increased anti-inflammatory cytokine secretion, decreased pro-inflammatory cytokine release, changes in cell membrane molecules expression and in metabolic pathways. Besides metabolically active MSCs and their secreted extracellular vesicles, non-viable and apoptotic MSCs or even MSC subcellular particles also exhibit immunosuppressive features that induce a regulatory phenotype in monocytes and macrophages. Indeed, the MSC modulation of monocyte and macrophage phenotype seems to be critical for therapy effectiveness in several disease models, since when these cells are depleted no immunosuppressive effects occur. Thus, here we review the effects of treatment with viable MSCs and MSC extracellular vesicles, further non-viable and apoptotic MSCs and MSC subcellular particles on macrophages and monocytes profile and its implications for immunoregulatory and reparative processes in different experimental models. Further, this work will include mechanisms of action exhibited in these different therapeutic approaches that induce anti-inflammatory properties in monocytes and macrophages.