Mesenchymal stem cells influence monocyte/macrophage phenotype: Regulatory mode and potential clinical applications - 13/08/23

Doi : 10.1016/j.biopha.2023.115042

Dejin Lu ^a,^{^{1
These authors contributed equally.}}, Xue Jiao ^a,^{^{1
These authors contributed equally.}}, Wenjian Jiang ^a, Li Yang ^a, Qian Gong ^a, Xiaobin Wang ^b,^⁎ , Minjie Wei ^a,^⁎ , Shiqiang Gong ^a,^⁎

^a Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China

^b Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China

^⁎ Corresponding authors.

Abstract

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from a variety of tissues, such as umbilical cord, fat, and bone marrow. Today, MSCs are widely recognized for their prominent anti-inflammatory properties in a variety of acute and chronic inflammatory diseases. In inflammatory diseases, monocytes/macrophages are an important part of the innate immune response in the body, and the alteration of the inflammatory phenotype plays a crucial role in the secretion of pro-inflammatory/anti-inflammatory factors, the repair of injured sites, and the infiltration of inflammatory cells. In this review, starting from the effect of MSCs on the monocyte/macrophage phenotype, we have outlined in detail the process by which MSCs influence the transformation of the monocyte/macrophage inflammatory phenotype, emphasizing the central role of monocytes/macrophages in MSC-mediated anti-inflammatory and damage site repair. MSCs are phagocytosed by monocytes/macrophages in various physiological states, the paracrine effect of MSCs and mitochondrial transfer of MSCs to macrophages to promote the transformation of monocytes/macrophages into anti-inflammatory phenotypes. We also review the clinical applications of the MSCs-monocytes/macrophages system and describe novel pathways between MSCs and tissue repair, the effects of MSCs on the adaptive immune system, and the effects of energy metabolism levels on monocyte/macrophage phenotypic changes.

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Graphical Abstract

Under inflammatory conditions, MSCs promote the transformation of macrophages from M1 type to M2 type through phagocytosis, paracrine effect, secretory vesicles and mitochondrial transfer.

Under inflammatory conditions, MSCs promote the transformation of macrophages from M1 type to M2 type through phagocytosis, paracrine effect, secretory vesicles and mitochondrial transfer. ga1

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Highlights

•	Mesenchymal stem cells convert monocytes/macrophages to an anti-inflammatory phenotype in three main ways.
•	Mesenchymal stem cells contribute to monocyte/macrophage phenotypic transformation through phagocytosis by monocytes/macrophages.
•	Paracrine actions of mesenchymal stem cells can induce monocytes/macrophages to switch to an anti-inflammatory phenotype.
•	Mitochondrial transfer from mesenchymal stem cells to macrophages can promote their conversion to an anti-inflammatory phenotype.

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Keywords : Mesenchymal stem cells, M1/M2 phenotype, Monocytes/macrophages, Phagocytosis, Paracrine action, Mitochondrial transfer

Abbreviations : MSCs, HLA-DR, ECM, IL-10, Ly6C, EVs, LPS, IDO, MPs, TNF-α, PGE2, CXCL12, Hb, MVs, TNTs, TLR4, PBMCs, NLRP3, CCR2, GVHD, KOA, SLE, RDEB, NSAIDs, PKM2