Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cells that have great potential as cell therapy for autoimmune and inflammatory disorders, as well as for other clinical conditions, due to their immunoregulatory and regenerative properties. MSCs modulate the inflammatory milieu by releasing soluble factors and acting through cell-to-cell mechanisms. MSCs switch the classical inflammatory status of monocytes and macrophages towards a nonclassical and anti-inflammatory phenotype. This is characterized by an increased secretion of anti-inflammatory cytokines, a decreased release of pro-inflammatory cytokines, and changes in the expression of cell membrane molecules and in metabolic pathways. The MSC modulation of monocyte and macrophage phenotypes seems to be critical for therapy effectiveness in several disease models, since when these cells are depleted, no immunoregulatory effects are observed. Here, we review the effects of living MSCs (metabolically active cells) and metabolically inactive MSCs (dead cells that lost metabolic activity by induced inactivation) and their derivatives (extracellular vesicles, soluble factors, extracts, and microparticles) on the profile of macrophages and monocytes and the implications for immunoregulatory and reparative processes. This review includes mechanisms of action exhibited in these different therapeutic appro-aches, which induce the antiinflammatory properties of monocytes and macrophages. Finally, we overview several possibilities of therapeutic applications of these cells and their derivatives, with results regarding monocytes and macrophages in animal model studies and some clinical trials.
|Number of pages||17|
|Journal||World Journal of Stem Cells|
|Publication status||Published - 26 Sept 2021|
Bibliographical noteFunding Information:
Supported by Fundo de Incentivo à Pesquisa e Eventos (Fipe) - Hospital de Clínicas de Porto Alegre, No. GPPG 2017-0004.
© The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.