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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

We previously demonstrated that neural stem/progenitor cells (NSPCs) were induced within and around the ischemic areas in a mouse model of ischemic stroke. These injury/ischemia-induced NSPCs (iNSPCs) differentiated to electrophysiologically functional neurons in vitro, indicating the presence of a self-repair system following injury. However, during the healing process after stroke, ischemic areas were gradually occupied by inflammatory cells, mainly microglial cells/macrophages (MGs/MΦs), and neurogenesis rarely occurred within and around the ischemic areas. Therefore, to achieve neural regeneration by utilizing endogenous iNSPCs, regulation of MGs/MΦs after an ischemic stroke might be necessary. To test this hypothesis, we used iNSPCs isolated from the ischemic areas after a stroke in our mouse model to investigate the role of MGs/MΦs in iNSPC regulation. In coculture experiments, we show that the presence of MGs/MΦs significantly reduces not only the proliferation but also the differentiation of iNSPCs toward neuronal cells, thereby preventing neurogenesis. These effects, however, are mitigated by MG/MΦ depletion using clodronate encapsulated in liposomes. Additionally, gene ontology analysis reveals that proliferation and neuronal differentiation are negatively regulated in iNSPCs cocultured with MGs/MΦs. These results indicate that MGs/MΦs negatively impact neurogenesis via iNSPCs, suggesting that the regulation of MGs/MΦs is essential to achieve iNSPC-based neural regeneration following an ischemic stroke.

Details

Title
Microglia Negatively Regulate the Proliferation and Neuronal Differentiation of Neural Stem/Progenitor Cells Isolated from Poststroke Mouse Brains
Author
Hirano, Yoshinobu 1 ; Nakagomi, Takayuki 2   VIAFID ORCID Logo  ; Nakano-Doi, Akiko 2 ; Kubo, Shuji 3   VIAFID ORCID Logo  ; Minato, Yusuke 4 ; Sawano, Toshinori 5   VIAFID ORCID Logo  ; Sakagami, Masafumi 1 ; Tsuzuki, Kenzo 1   VIAFID ORCID Logo 

 Department of Otorhinolaryngology—Head & Neck Surgery, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya 663-8501, Japan; [email protected] (Y.H.); [email protected] (M.S.); [email protected] (K.T.) 
 Institute for Advanced Medical Sciences, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan; [email protected] (A.N.-D.); [email protected] (S.K.); Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan 
 Institute for Advanced Medical Sciences, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan; [email protected] (A.N.-D.); [email protected] (S.K.) 
 Department of Anatomy and Cell Biology, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan; [email protected] 
 Department of Biomedical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu 525-8577, Japan; [email protected] 
First page
2040
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20734409
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2856875665
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.