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Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation

Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to ha...

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Autores principales: Yan, Ke, Zhang, Run, Sun, Chengmei, Chen, Lei, Li, Peng, Liu, Yi, Peng, Lingmei, Sun, Haitao, Qin, Kun, Chen, Fanfan, Huang, Weiyi, Chen, Yuxin, Lv, Bingke, Du, Mouxuan, Zou, Yuxi, Cai, Yingqian, Qin, Lingsha, Tang, Yanping, Jiang, Xiaodan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877190/
https://www.ncbi.nlm.nih.gov/pubmed/24391898
http://dx.doi.org/10.1371/journal.pone.0084116
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author Yan, Ke
Zhang, Run
Sun, Chengmei
Chen, Lei
Li, Peng
Liu, Yi
Peng, Lingmei
Sun, Haitao
Qin, Kun
Chen, Fanfan
Huang, Weiyi
Chen, Yuxin
Lv, Bingke
Du, Mouxuan
Zou, Yuxi
Cai, Yingqian
Qin, Lingsha
Tang, Yanping
Jiang, Xiaodan
author_facet Yan, Ke
Zhang, Run
Sun, Chengmei
Chen, Lei
Li, Peng
Liu, Yi
Peng, Lingmei
Sun, Haitao
Qin, Kun
Chen, Fanfan
Huang, Weiyi
Chen, Yuxin
Lv, Bingke
Du, Mouxuan
Zou, Yuxi
Cai, Yingqian
Qin, Lingsha
Tang, Yanping
Jiang, Xiaodan
author_sort Yan, Ke
collection PubMed
description Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS), and then culturing these microglia with BMSC-conditioned medium (BMSC-CM). We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO) were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation.
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spelling pubmed-38771902014-01-03 Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation Yan, Ke Zhang, Run Sun, Chengmei Chen, Lei Li, Peng Liu, Yi Peng, Lingmei Sun, Haitao Qin, Kun Chen, Fanfan Huang, Weiyi Chen, Yuxin Lv, Bingke Du, Mouxuan Zou, Yuxi Cai, Yingqian Qin, Lingsha Tang, Yanping Jiang, Xiaodan PLoS One Research Article Many studies have shown that microglia in the activated state may be neurotoxic. It has been proven that uncontrolled or over-activated microglia play an important role in many neurodegenerative disorders. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown in many animal models to have a therapeutic effect on neural damage. Such a therapeutic effect is attributed to the fact that BMSCs have the ability to differentiate into neurons and to produce trophic factors, but there is little information available in the literature concerning whether BMSCs play a therapeutic role by affecting microglial activity. In this study, we triggered an inflammatory response situation in vitro by stimulating microglia with the bacterial endotoxin lipopolysaccharide (LPS), and then culturing these microglia with BMSC-conditioned medium (BMSC-CM). We found that BMSC-CM significantly inhibited proliferation and secretion of pro-inflammatory factors by activated microglia. Furthermore, we found that the phagocytic capacity of microglia was also inhibited by BMSC-CM. Finally, we investigated whether the induction of apoptosis and the production of nitric oxide (NO) were involved in the inhibition of microglial activation. We found that BMSC-CM significantly induced apoptosis of microglia, while no apoptosis was apparent in the LPS-stimulated microglia. Our study also provides evidence that NO participates in the inhibitory effect of BMSCs. Our experimental results provide evidence that BMSCs have the ability to maintain the resting phenotype of microglia or to control microglial activation through their production of several factors, indicating that BMSCs could be a promising therapeutic tool for treatment of diseases associated with microglial activation. Public Library of Science 2013-12-31 /pmc/articles/PMC3877190/ /pubmed/24391898 http://dx.doi.org/10.1371/journal.pone.0084116 Text en © 2013 Yan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yan, Ke
Zhang, Run
Sun, Chengmei
Chen, Lei
Li, Peng
Liu, Yi
Peng, Lingmei
Sun, Haitao
Qin, Kun
Chen, Fanfan
Huang, Weiyi
Chen, Yuxin
Lv, Bingke
Du, Mouxuan
Zou, Yuxi
Cai, Yingqian
Qin, Lingsha
Tang, Yanping
Jiang, Xiaodan
Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title_full Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title_fullStr Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title_full_unstemmed Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title_short Bone Marrow-Derived Mesenchymal Stem Cells Maintain the Resting Phenotype of Microglia and Inhibit Microglial Activation
title_sort bone marrow-derived mesenchymal stem cells maintain the resting phenotype of microglia and inhibit microglial activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877190/
https://www.ncbi.nlm.nih.gov/pubmed/24391898
http://dx.doi.org/10.1371/journal.pone.0084116
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