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NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke
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Lan, Xiao-Yan, Liang, Xue-Song, Cao, Ming-Xuan, Qin, Hua-Min, Chu, Cheng-Yan, Boltze, Johannes and Li, Shen (2024) NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke. Journal of Cerebral Blood Flow & Metabolism . doi:10.1177/0271678X241226482 ISSN 0271-678X. (In Press)
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Official URL: http://dx.doi.org/10.1177/0271678X241226482
Abstract
The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation.
Item Type: | Journal Article | ||||||||||||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Cerebral ischemia, Mesenchymal stem cells, Bone marrow cells , Cell adhesion molecules, Cerebrovascular disease, Cerebrovascular disease -- Treatment | ||||||||||||||||||||||||
Journal or Publication Title: | Journal of Cerebral Blood Flow & Metabolism | ||||||||||||||||||||||||
Publisher: | SAGE Publications | ||||||||||||||||||||||||
ISSN: | 0271-678X | ||||||||||||||||||||||||
Official Date: | 17 January 2024 | ||||||||||||||||||||||||
Dates: |
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DOI: | 10.1177/0271678X241226482 | ||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||
Publication Status: | In Press | ||||||||||||||||||||||||
Re-use Statement: | Lan, Xiao-Yan, Liang, Xue-Song, Cao, Ming-Xuan, Qin, Hua-Min, Chu, Cheng-Yan, Boltze, Johannes and Li, Shen (2024) NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke. Journal of Cerebral Blood Flow & Metabolism. Copyright © The Author(s) 2024. Reprinted by permission of SAGE Publications. http://dx.doi.org/10.1177/0271678X241226482 | ||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||
Date of first compliant deposit: | 17 January 2024 | ||||||||||||||||||||||||
Date of first compliant Open Access: | 19 January 2024 | ||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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