Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion

BACKGROUND: Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in ischemic brain injury, but the underlying mechanism is poorly understood. The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemi...

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Autores principales: Hu, Xiaowen, Pan, Jiaji, Li, Yongfang, Jiang, Yixu, Zheng, Haoran, Shi, Rubing, Zhang, Qi, Liu, Chang, Tian, Hengli, Zhang, Zhijun, Tang, Yaohui, Yang, Guo-Yuan, Wang, Yongting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772170/
https://www.ncbi.nlm.nih.gov/pubmed/35057862
http://dx.doi.org/10.1186/s13287-021-02668-0
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author Hu, Xiaowen
Pan, Jiaji
Li, Yongfang
Jiang, Yixu
Zheng, Haoran
Shi, Rubing
Zhang, Qi
Liu, Chang
Tian, Hengli
Zhang, Zhijun
Tang, Yaohui
Yang, Guo-Yuan
Wang, Yongting
author_facet Hu, Xiaowen
Pan, Jiaji
Li, Yongfang
Jiang, Yixu
Zheng, Haoran
Shi, Rubing
Zhang, Qi
Liu, Chang
Tian, Hengli
Zhang, Zhijun
Tang, Yaohui
Yang, Guo-Yuan
Wang, Yongting
author_sort Hu, Xiaowen
collection PubMed
description BACKGROUND: Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in ischemic brain injury, but the underlying mechanism is poorly understood. The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemia. METHODS: After the intravenous injection of ADSC-EVs, therapeutic efficacy was evaluated by neurobehavioral tests and brain atrophy volume. The polarization of microglia was assessed by immunostaining and qPCR. We further performed miRNA sequencing of ADSC-EVs and analyzed the relationship between the upregulated miRNAs in ADSC-EVs and microglial polarization-related proteins using Ingenuity Pathway Analysis (IPA). RESULTS: The results showed that ADSC-EVs reduced brain atrophy volume, improved neuromotor and cognitive functions after mouse ischemic stroke. The loss of oligodendrocytes was attenuated after ADSC-EVs injection. The number of blood vessels, as well as newly proliferated endothelial cells in the peri-ischemia area were higher in the ADSC-EVs treated group than that in the PBS group. In addition, ADSC-EVs regulated the polarization of microglia, resulting in increased repair-promoting M2 phenotype and decreased pro-inflammatory M1 phenotype. Finally, STAT1 and PTEN were highlighted as two downstream targets of up-regulated miRNAs in ADSC-EVs among 85 microglia/macrophage polarization related proteins by IPA. The inhibition of STAT1 and PTEN by ADSC-EVs were confirmed in cultured microglia. CONCLUSIONS: In summary, ADSC-EVs reduced ischemic brain injury, which was associated with the regulation of microglial polarization. miRNAs in ADSC-EVs partly contributed to their function in regulating microglial polarization by targeting PTEN and STAT1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02668-0.
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spelling pubmed-87721702022-01-20 Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion Hu, Xiaowen Pan, Jiaji Li, Yongfang Jiang, Yixu Zheng, Haoran Shi, Rubing Zhang, Qi Liu, Chang Tian, Hengli Zhang, Zhijun Tang, Yaohui Yang, Guo-Yuan Wang, Yongting Stem Cell Res Ther Research BACKGROUND: Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in ischemic brain injury, but the underlying mechanism is poorly understood. The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemia. METHODS: After the intravenous injection of ADSC-EVs, therapeutic efficacy was evaluated by neurobehavioral tests and brain atrophy volume. The polarization of microglia was assessed by immunostaining and qPCR. We further performed miRNA sequencing of ADSC-EVs and analyzed the relationship between the upregulated miRNAs in ADSC-EVs and microglial polarization-related proteins using Ingenuity Pathway Analysis (IPA). RESULTS: The results showed that ADSC-EVs reduced brain atrophy volume, improved neuromotor and cognitive functions after mouse ischemic stroke. The loss of oligodendrocytes was attenuated after ADSC-EVs injection. The number of blood vessels, as well as newly proliferated endothelial cells in the peri-ischemia area were higher in the ADSC-EVs treated group than that in the PBS group. In addition, ADSC-EVs regulated the polarization of microglia, resulting in increased repair-promoting M2 phenotype and decreased pro-inflammatory M1 phenotype. Finally, STAT1 and PTEN were highlighted as two downstream targets of up-regulated miRNAs in ADSC-EVs among 85 microglia/macrophage polarization related proteins by IPA. The inhibition of STAT1 and PTEN by ADSC-EVs were confirmed in cultured microglia. CONCLUSIONS: In summary, ADSC-EVs reduced ischemic brain injury, which was associated with the regulation of microglial polarization. miRNAs in ADSC-EVs partly contributed to their function in regulating microglial polarization by targeting PTEN and STAT1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02668-0. BioMed Central 2022-01-20 /pmc/articles/PMC8772170/ /pubmed/35057862 http://dx.doi.org/10.1186/s13287-021-02668-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hu, Xiaowen
Pan, Jiaji
Li, Yongfang
Jiang, Yixu
Zheng, Haoran
Shi, Rubing
Zhang, Qi
Liu, Chang
Tian, Hengli
Zhang, Zhijun
Tang, Yaohui
Yang, Guo-Yuan
Wang, Yongting
Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title_full Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title_fullStr Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title_full_unstemmed Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title_short Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
title_sort extracellular vesicles from adipose-derived stem cells promote microglia m2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772170/
https://www.ncbi.nlm.nih.gov/pubmed/35057862
http://dx.doi.org/10.1186/s13287-021-02668-0
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