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Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, i...

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Autores principales: Lim, Jung Yeon, Lee, Jung Eun, Park, Soon A, Park, Sang In, Yon, Jung-Min, Park, Jeong-Ah, Jeun, Sin-Soo, Kim, Seung Joon, Lee, Hong Jun, Kim, Sung Won, Yang, Seung Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947560/
https://www.ncbi.nlm.nih.gov/pubmed/35326480
http://dx.doi.org/10.3390/cells11061029
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author Lim, Jung Yeon
Lee, Jung Eun
Park, Soon A
Park, Sang In
Yon, Jung-Min
Park, Jeong-Ah
Jeun, Sin-Soo
Kim, Seung Joon
Lee, Hong Jun
Kim, Sung Won
Yang, Seung Ho
author_facet Lim, Jung Yeon
Lee, Jung Eun
Park, Soon A
Park, Sang In
Yon, Jung-Min
Park, Jeong-Ah
Jeun, Sin-Soo
Kim, Seung Joon
Lee, Hong Jun
Kim, Sung Won
Yang, Seung Ho
author_sort Lim, Jung Yeon
collection PubMed
description The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ(1–42)) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ(1–42) induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ(1–42) exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ(1–42). Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.
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spelling pubmed-89475602022-03-25 Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease Lim, Jung Yeon Lee, Jung Eun Park, Soon A Park, Sang In Yon, Jung-Min Park, Jeong-Ah Jeun, Sin-Soo Kim, Seung Joon Lee, Hong Jun Kim, Sung Won Yang, Seung Ho Cells Article The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ(1–42)) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ(1–42) induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ(1–42) exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ(1–42). Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD. MDPI 2022-03-18 /pmc/articles/PMC8947560/ /pubmed/35326480 http://dx.doi.org/10.3390/cells11061029 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Lim, Jung Yeon
Lee, Jung Eun
Park, Soon A
Park, Sang In
Yon, Jung-Min
Park, Jeong-Ah
Jeun, Sin-Soo
Kim, Seung Joon
Lee, Hong Jun
Kim, Sung Won
Yang, Seung Ho
Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title_full Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title_fullStr Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title_full_unstemmed Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title_short Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
title_sort protective effect of human-neural-crest-derived nasal turbinate stem cells against amyloid-β neurotoxicity through inhibition of osteopontin in a human cerebral organoid model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947560/
https://www.ncbi.nlm.nih.gov/pubmed/35326480
http://dx.doi.org/10.3390/cells11061029
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