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Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway

BACKGROUND: Intracerebral hemorrhage (ICH) is a severe brain-injured disease accompanied by cerebral edema, inflammation, and subsequent neurological deficits. Mesenchymal stem cells (MSCs) transplantation has been used as a neuroprotective therapy in nervous system diseases because of its anti-infl...

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Autores principales: Yang, Guoqiang, Kantapan, Jiraporn, Mazhar, Maryam, Bai, Xue, Zou, Yuanxia, Wang, Honglian, Huang, Bingfeng, Yang, Sijing, Dechsupa, Nathupakorn, Wang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186667/
https://www.ncbi.nlm.nih.gov/pubmed/37189208
http://dx.doi.org/10.1186/s13287-023-03369-6
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author Yang, Guoqiang
Kantapan, Jiraporn
Mazhar, Maryam
Bai, Xue
Zou, Yuanxia
Wang, Honglian
Huang, Bingfeng
Yang, Sijing
Dechsupa, Nathupakorn
Wang, Li
author_facet Yang, Guoqiang
Kantapan, Jiraporn
Mazhar, Maryam
Bai, Xue
Zou, Yuanxia
Wang, Honglian
Huang, Bingfeng
Yang, Sijing
Dechsupa, Nathupakorn
Wang, Li
author_sort Yang, Guoqiang
collection PubMed
description BACKGROUND: Intracerebral hemorrhage (ICH) is a severe brain-injured disease accompanied by cerebral edema, inflammation, and subsequent neurological deficits. Mesenchymal stem cells (MSCs) transplantation has been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. Nevertheless, the biological characteristics of transplanted MSCs, including the survival rate, viability, and effectiveness, are restricted because of the severe inflammatory response after ICH. Therefore, improving the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the biomedical applications of coordination chemistry-mediated metal-quercetin complex have been verified positively and studied extensively, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) possesses extraordinary dual capabilities with a stimulating agent for cell growth and an imaging probe by magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH while also labeling MSCs for their tracking by MRI. This study aimed to explore the effects of MSCs with IronQ in regulating inflammation and further clarify their potential mechanisms. METHODS: C57BL/6 male mice were utilized in this research. A collagenase I-induced ICH mice model was established and randomly separated into the model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ) after 24 h. Then, the neurological deficits score, brain water content (BWC), and protein expression, such as TNF-α, IL-6, NeuN, MBP, as well as GFAP, were investigated. We further measured the protein expression of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells were utilized to investigate the neuroprotection of conditioned medium of MSCs co-cultured with IronQ in vitro. RESULTS: We found that the combined treatment of MSCs with IronQ improved the inflammation-induced neurological deficits and BWC in vivo by inhibiting the Mincle/syk signaling pathway. Conditioned medium derived from MSCs co-cultured with IronQ decreased inflammation, Mincle, and its downstream targets in the LPS-induced BV2 cell line. CONCLUSIONS: These data suggested that the combined treatment exerts a collaborative effect in alleviating ICH-induced inflammatory response through the downregulation of the Mincle/syk signaling pathway following ICH, further improving the neurologic deficits and brain edema. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03369-6.
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spelling pubmed-101866672023-05-17 Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway Yang, Guoqiang Kantapan, Jiraporn Mazhar, Maryam Bai, Xue Zou, Yuanxia Wang, Honglian Huang, Bingfeng Yang, Sijing Dechsupa, Nathupakorn Wang, Li Stem Cell Res Ther Research BACKGROUND: Intracerebral hemorrhage (ICH) is a severe brain-injured disease accompanied by cerebral edema, inflammation, and subsequent neurological deficits. Mesenchymal stem cells (MSCs) transplantation has been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. Nevertheless, the biological characteristics of transplanted MSCs, including the survival rate, viability, and effectiveness, are restricted because of the severe inflammatory response after ICH. Therefore, improving the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the biomedical applications of coordination chemistry-mediated metal-quercetin complex have been verified positively and studied extensively, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) possesses extraordinary dual capabilities with a stimulating agent for cell growth and an imaging probe by magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH while also labeling MSCs for their tracking by MRI. This study aimed to explore the effects of MSCs with IronQ in regulating inflammation and further clarify their potential mechanisms. METHODS: C57BL/6 male mice were utilized in this research. A collagenase I-induced ICH mice model was established and randomly separated into the model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ) after 24 h. Then, the neurological deficits score, brain water content (BWC), and protein expression, such as TNF-α, IL-6, NeuN, MBP, as well as GFAP, were investigated. We further measured the protein expression of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells were utilized to investigate the neuroprotection of conditioned medium of MSCs co-cultured with IronQ in vitro. RESULTS: We found that the combined treatment of MSCs with IronQ improved the inflammation-induced neurological deficits and BWC in vivo by inhibiting the Mincle/syk signaling pathway. Conditioned medium derived from MSCs co-cultured with IronQ decreased inflammation, Mincle, and its downstream targets in the LPS-induced BV2 cell line. CONCLUSIONS: These data suggested that the combined treatment exerts a collaborative effect in alleviating ICH-induced inflammatory response through the downregulation of the Mincle/syk signaling pathway following ICH, further improving the neurologic deficits and brain edema. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03369-6. BioMed Central 2023-05-15 /pmc/articles/PMC10186667/ /pubmed/37189208 http://dx.doi.org/10.1186/s13287-023-03369-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Yang, Guoqiang
Kantapan, Jiraporn
Mazhar, Maryam
Bai, Xue
Zou, Yuanxia
Wang, Honglian
Huang, Bingfeng
Yang, Sijing
Dechsupa, Nathupakorn
Wang, Li
Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title_full Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title_fullStr Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title_full_unstemmed Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title_short Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway
title_sort mesenchymal stem cells transplantation combined with ironq attenuates ich-induced inflammation response via mincle/syk signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186667/
https://www.ncbi.nlm.nih.gov/pubmed/37189208
http://dx.doi.org/10.1186/s13287-023-03369-6
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