Sant'Ana AN, Araújo AB, Gonçalves FDC, Paz AH. Effects of living and metabolically inactive mesenchymal stromal cells and their derivatives on monocytes and macrophages. World J Stem Cells 2021; 13(9): 1160-1176 [PMID: 34630856 DOI: 10.4252/wjsc.v13.i9.1160]
Corresponding Author of This Article
Anelise Bergmann Araújo, DSc, Research Scientist, Technician, Centro de Processamento Celular, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903, RS, Brazil. anelise_araujo@yahoo.com.br
Research Domain of This Article
Cell Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Sep 26, 2021; 13(9): 1160-1176 Published online Sep 26, 2021. doi: 10.4252/wjsc.v13.i9.1160
Effects of living and metabolically inactive mesenchymal stromal cells and their derivatives on monocytes and macrophages
Alexia Nedel Sant'Ana, Anelise Bergmann Araújo, Fabiany da Costa Gonçalves, Ana Helena Paz
Alexia Nedel Sant'Ana, Ana Helena Paz, Laboratório de Células Tecidos e Genes, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil
Anelise Bergmann Araújo, Centro de Processamento Celular, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil
Fabiany da Costa Gonçalves, Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GD, Netherlands
Ana Helena Paz, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil
Author contributions: Sant’Ana AN, Araújo AB, Gonçalves FDC and Paz AH performed data collection, wrote and revised the paper.
Supported byFundo de Incentivo à Pesquisa e Eventos (Fipe) - Hospital de Clínicas de Porto Alegre, No. GPPG 2017-0004.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anelise Bergmann Araújo, DSc, Research Scientist, Technician, Centro de Processamento Celular, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903, RS, Brazil. anelise_araujo@yahoo.com.br
Received: February 23, 2021 Peer-review started: February 23, 2021 First decision: April 20, 2021 Revised: May 1, 2021 Accepted: September 3, 2021 Article in press: September 3, 2021 Published online: September 26, 2021
Abstract
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 non-classical 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 approaches, which induce the anti-inflammatory 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.
Core Tip: Mesenchymal stromal cells (MSCs) and their derivatives possess immunoregulatory and regenerative properties that involve the classical activation of monocytes and macrophages towards an anti-inflammatory profile, marked by the secretion of anti-inflammatory and reparative factors that guide the inflammation resolution and healing processes. This review will comprise the effects of living and metabolically inactive MSCs, MSC extracellular vesicles, subcellular microparticles, and cell extracts on monocytes and macrophages, as well as several possibilities of therapeutic applications.
