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World J Stem Cells. Aug 26, 2021; 13(8): 1030-1048
Published online Aug 26, 2021. doi: 10.4252/wjsc.v13.i8.1030
Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia
Wen-Qiang Xin, Wei Wei, Yong-Li Pan, Bao-Long Cui, Xin-Yu Yang, Mathias Bähr, Thorsten R Doeppner
Wen-Qiang Xin, Wei Wei, Yong-Li Pan, Bao-Long Cui, Mathias Bähr, Thorsten R Doeppner, Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
Xin-Yu Yang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
Author contributions: Xin WQ and Doeppner TR designed and conceptualized the article; Xin WQ and Wei W prepared the figures and tables; all authors significantly contributed to writing the paper and provided important intellectual content.
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: Thorsten R Doeppner, MD, MSc, Professor, Department of Neurology, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. thorsten.doeppner@med.uni-goettingen.de
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 5, 2021
Revised: May 25, 2021
Accepted: August 6, 2021
Article in press: August 6, 2021
Published online: August 26, 2021
Processing time: 156 Days and 9 Hours
Abstract

Inflammation plays an important role in the pathological process of ischemic stroke, and systemic inflammation affects patient prognosis. As resident immune cells in the brain, microglia are significantly involved in immune defense and tissue repair under various pathological conditions, including cerebral ischemia. Although the differentiation of M1 and M2 microglia is certainly oversimplified, changing the activation state of microglia appears to be an intriguing therapeutic strategy for cerebral ischemia. Recent evidence indicates that both mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) regulate inflammation and modify tissue repair under preclinical stroke conditions. However, the precise mechanisms of these signaling pathways, especially in the context of the mutual interaction between MSCs or MSC-derived EVs and resident microglia, have not been sufficiently unveiled. Hence, this review summarizes the state-of-the-art knowledge on MSC- and MSC-EV-mediated regulation of microglial activity under ischemic stroke conditions with respect to various signaling pathways, including cytokines, neurotrophic factors, transcription factors, and microRNAs.

Keywords: Extracellular vesicles; Mesenchymal stem cells; Microglial activation; M2 polarization; Ischemic stroke

Core Tip: Upon stroke induction, M1 microglia participate in the proinflammatory tissue response, whereas M2 microglia promote brain repair by secreting anti-inflammatory cytokines and neurotrophic factors. This review summarizes the effects of mesenchymal stem cells (MSCs) and MSC-extracellular vesicles on regulating microglial activity under ischemic stroke conditions through various signaling pathways, such as cytokines, neurotrophic factors, transcription factors, and microRNAs.