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Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke

BACKGROUND: Manipulating the immune inflammatory response after cerebral ischemia has been a novel therapeutic strategy for ischemic stroke. This study attempted to investigate the effects of the transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells (HCB-SCs...

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Autores principales: Zhao, Yanxin, Zhu, Tianrui, Li, Heng, Zhao, Jing, Li, Xiaohong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927491/
https://www.ncbi.nlm.nih.gov/pubmed/31908436
http://dx.doi.org/10.2147/CIA.S223595
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author Zhao, Yanxin
Zhu, Tianrui
Li, Heng
Zhao, Jing
Li, Xiaohong
author_facet Zhao, Yanxin
Zhu, Tianrui
Li, Heng
Zhao, Jing
Li, Xiaohong
author_sort Zhao, Yanxin
collection PubMed
description BACKGROUND: Manipulating the immune inflammatory response after cerebral ischemia has been a novel therapeutic strategy for ischemic stroke. This study attempted to investigate the effects of the transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells (HCB-SCs) on the inflammatory response in transient middle cerebral occlusion (tMCAO) rats. METHODS: The tMCAO rats were subjected to the transplantation of lymphocytes co-cultured with HCB-SCs through tail vein injection. Infarct size and neurological deficits were measured at 48 hrs after stroke. Neurological deficits were assessed using Bederson’s scoring system and tape removal test. Blood T cell flow cytometry was performed to measure the differentiation of regulatory T cells (Tregs). Western blot was used to detect the protein levels of inflammation-related molecules, apoptosis-related molecule, and signaling molecules in ischemic brain. TUNEL staining was performed to analyze cell apoptosis in ischemic cerebral cortex. RESULTS: The transplantation of lymphocytes co-cultured with HCB-SCs significantly improved the neurological defects, reduced ischemic brain damage, and increased the proportion of peripheral CD4(+)CD25(+)Foxp3(+) Tregs. Meanwhile, the transplantation of co-cultured cells decreased the expression of NLRP3 inflammasome and associated factors, such as caspase-1 and IL-1β, and inhibited the activation of NF-κB, ERK and caspase-3 in ischemic brain. The co-cultured cells significantly decreased the number of tMCAO-induced cell apoptosis. CONCLUSION: Lymphocytes co-cultured with HCB-SCs exhibit a neuroprotective effect after ischemic stroke by promoting Tregs differentiation and suppressing NLRP3 inflammasome activation and neuron apoptosis, and might be a promising therapeutic strategy for ischemic stroke.
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spelling pubmed-69274912020-01-06 Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke Zhao, Yanxin Zhu, Tianrui Li, Heng Zhao, Jing Li, Xiaohong Clin Interv Aging Original Research BACKGROUND: Manipulating the immune inflammatory response after cerebral ischemia has been a novel therapeutic strategy for ischemic stroke. This study attempted to investigate the effects of the transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells (HCB-SCs) on the inflammatory response in transient middle cerebral occlusion (tMCAO) rats. METHODS: The tMCAO rats were subjected to the transplantation of lymphocytes co-cultured with HCB-SCs through tail vein injection. Infarct size and neurological deficits were measured at 48 hrs after stroke. Neurological deficits were assessed using Bederson’s scoring system and tape removal test. Blood T cell flow cytometry was performed to measure the differentiation of regulatory T cells (Tregs). Western blot was used to detect the protein levels of inflammation-related molecules, apoptosis-related molecule, and signaling molecules in ischemic brain. TUNEL staining was performed to analyze cell apoptosis in ischemic cerebral cortex. RESULTS: The transplantation of lymphocytes co-cultured with HCB-SCs significantly improved the neurological defects, reduced ischemic brain damage, and increased the proportion of peripheral CD4(+)CD25(+)Foxp3(+) Tregs. Meanwhile, the transplantation of co-cultured cells decreased the expression of NLRP3 inflammasome and associated factors, such as caspase-1 and IL-1β, and inhibited the activation of NF-κB, ERK and caspase-3 in ischemic brain. The co-cultured cells significantly decreased the number of tMCAO-induced cell apoptosis. CONCLUSION: Lymphocytes co-cultured with HCB-SCs exhibit a neuroprotective effect after ischemic stroke by promoting Tregs differentiation and suppressing NLRP3 inflammasome activation and neuron apoptosis, and might be a promising therapeutic strategy for ischemic stroke. Dove 2019-12-19 /pmc/articles/PMC6927491/ /pubmed/31908436 http://dx.doi.org/10.2147/CIA.S223595 Text en © 2019 Zhao et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhao, Yanxin
Zhu, Tianrui
Li, Heng
Zhao, Jing
Li, Xiaohong
Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title_full Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title_fullStr Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title_full_unstemmed Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title_short Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke
title_sort transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells attenuates inflammasome activity in ischemic stroke
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927491/
https://www.ncbi.nlm.nih.gov/pubmed/31908436
http://dx.doi.org/10.2147/CIA.S223595
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