Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy

Abstract Subarachnoid hemorrhage (SAH) can lead to significant acute neuroinflammation, with treatment outcomes often being inadequate. Olfactory mucosa mesenchymal stem cells (OM‐MSCs) have promising therapeutic potential in nerve regeneration and functional recovery. This investigation sought to e...

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Main Authors: Jian Wang, Jun Peng, Ling Gao, Jun He, Long Lin, Jia‐Meng Li, Ying Xia
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Kaohsiung Journal of Medical Sciences
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Online Access:https://doi.org/10.1002/kjm2.12951
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author Jian Wang
Jun Peng
Ling Gao
Jun He
Long Lin
Jia‐Meng Li
Ying Xia
author_facet Jian Wang
Jun Peng
Ling Gao
Jun He
Long Lin
Jia‐Meng Li
Ying Xia
author_sort Jian Wang
collection DOAJ
description Abstract Subarachnoid hemorrhage (SAH) can lead to significant acute neuroinflammation, with treatment outcomes often being inadequate. Olfactory mucosa mesenchymal stem cells (OM‐MSCs) have promising therapeutic potential in nerve regeneration and functional recovery. This investigation sought to elucidate the functional mechanisms through which exosomes derived from OM‐MSCs provide protection against neuroinflammation following SAH. Mouse OM‐MSCs and their exosomes were isolated and characterized using various techniques, including transmission electron microscopy, immunofluorescence staining, Western blotting, flow cytometry, and nanoparticle tracking analysis. Hemin‐induced HT22 cells were subsequently utilized to assess the impact of OM‐MSC‐derived exosomes on the inflammatory response, apoptosis, and mitophagy through ELISAs, Western blotting, qPCR, flow cytometry, and immunofluorescence staining. The impacts of exosomes on neuroinflammation and neuronal damage in SAH model mice were assessed using qPCR, ELISAs, Western blotting, immunofluorescence staining, and TUNEL staining. Exosomes derived from OM‐MSCs had the capacity to reduce the levels of proinflammatory factors (IL‐6, IL‐1β, and TNF‐α) and promote apoptosis in hemin‐induced HT22 cells. Exosomes alleviated neuroinflammation and neuronal injury post‐SAH, as evidenced by the increase in modified Garcia scores, reduction in the brain water content, decrease in blood–brain barrier permeability, decreases in inflammatory marker levels, and reduction in apoptosis rates. Notably, the protective effects of exosomes derived from OM‐MSCs on neuroinflammation and apoptosis, both in vitro and in vivo, were mediated via the activation of mitophagy. These findings provide a fresh perspective for subsequent clinical research in the domain of prevention and treatment strategies.
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spelling doaj-art-124d23c053e54901a231dfa9cbc0c08a2025-08-20T01:54:54ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502025-04-01414n/an/a10.1002/kjm2.12951Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagyJian Wang0Jun Peng1Ling Gao2Jun He3Long Lin4Jia‐Meng Li5Ying Xia6Department of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaDepartment of Neurosurgery Haikou Affiliated Hospital of Central South University Xiangya School of Medicine Haikou Hainan Province People's Republic of ChinaAbstract Subarachnoid hemorrhage (SAH) can lead to significant acute neuroinflammation, with treatment outcomes often being inadequate. Olfactory mucosa mesenchymal stem cells (OM‐MSCs) have promising therapeutic potential in nerve regeneration and functional recovery. This investigation sought to elucidate the functional mechanisms through which exosomes derived from OM‐MSCs provide protection against neuroinflammation following SAH. Mouse OM‐MSCs and their exosomes were isolated and characterized using various techniques, including transmission electron microscopy, immunofluorescence staining, Western blotting, flow cytometry, and nanoparticle tracking analysis. Hemin‐induced HT22 cells were subsequently utilized to assess the impact of OM‐MSC‐derived exosomes on the inflammatory response, apoptosis, and mitophagy through ELISAs, Western blotting, qPCR, flow cytometry, and immunofluorescence staining. The impacts of exosomes on neuroinflammation and neuronal damage in SAH model mice were assessed using qPCR, ELISAs, Western blotting, immunofluorescence staining, and TUNEL staining. Exosomes derived from OM‐MSCs had the capacity to reduce the levels of proinflammatory factors (IL‐6, IL‐1β, and TNF‐α) and promote apoptosis in hemin‐induced HT22 cells. Exosomes alleviated neuroinflammation and neuronal injury post‐SAH, as evidenced by the increase in modified Garcia scores, reduction in the brain water content, decrease in blood–brain barrier permeability, decreases in inflammatory marker levels, and reduction in apoptosis rates. Notably, the protective effects of exosomes derived from OM‐MSCs on neuroinflammation and apoptosis, both in vitro and in vivo, were mediated via the activation of mitophagy. These findings provide a fresh perspective for subsequent clinical research in the domain of prevention and treatment strategies.https://doi.org/10.1002/kjm2.12951exosomesmitophagyneuroinflammationolfactory mucosa mesenchymal stem cellssubarachnoid hemorrhage
spellingShingle Jian Wang
Jun Peng
Ling Gao
Jun He
Long Lin
Jia‐Meng Li
Ying Xia
Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
Kaohsiung Journal of Medical Sciences
exosomes
mitophagy
neuroinflammation
olfactory mucosa mesenchymal stem cells
subarachnoid hemorrhage
title Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
title_full Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
title_fullStr Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
title_full_unstemmed Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
title_short Olfactory mucosa mesenchymal stem cell‐derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
title_sort olfactory mucosa mesenchymal stem cell derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy
topic exosomes
mitophagy
neuroinflammation
olfactory mucosa mesenchymal stem cells
subarachnoid hemorrhage
url https://doi.org/10.1002/kjm2.12951
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AT junhe olfactorymucosamesenchymalstemcellderivedexosomesprotectagainstneuroinflammationaftersubarachnoidhemorrhagebyactivatingmitophagy
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