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Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation

The remarkable advancements related to cerebral organoids have provided unprecedented opportunities to model human brain development and diseases. However, despite their potential significance in neurodegenerative diseases such as Parkinson’s disease (PD), the role of exosomes from cerebral organoid...

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Autores principales: Ji, Xingrui, Zhou, Shaocong, Wang, Nana, Wang, Jingwen, Wu, Yue, Duan, Yuhan, Ni, Penghao, Zhang, Jingzhong, Yu, Shuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341736/
https://www.ncbi.nlm.nih.gov/pubmed/37446226
http://dx.doi.org/10.3390/ijms241311048
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author Ji, Xingrui
Zhou, Shaocong
Wang, Nana
Wang, Jingwen
Wu, Yue
Duan, Yuhan
Ni, Penghao
Zhang, Jingzhong
Yu, Shuang
author_facet Ji, Xingrui
Zhou, Shaocong
Wang, Nana
Wang, Jingwen
Wu, Yue
Duan, Yuhan
Ni, Penghao
Zhang, Jingzhong
Yu, Shuang
author_sort Ji, Xingrui
collection PubMed
description The remarkable advancements related to cerebral organoids have provided unprecedented opportunities to model human brain development and diseases. However, despite their potential significance in neurodegenerative diseases such as Parkinson’s disease (PD), the role of exosomes from cerebral organoids (OExo) has been largely unknown. In this study, we compared the effects of OExo to those of mesenchymal stem cell (MSC)-derived exosomes (CExo) and found that OExo shared similar neuroprotective effects to CExo. Our findings showed that OExo mitigated H(2)O(2)-induced oxidative stress and apoptosis in rat midbrain astrocytes by reducing excess ROS production, antioxidant depletion, lipid peroxidation, mitochondrial dysfunction, and the expression of pro-apoptotic genes. Notably, OExo demonstrated superiority over CExo in promoting the differentiation of human-induced pluripotent stem cells (iPSCs) into dopaminergic (DA) neurons. This was attributed to the higher abundance of neurotrophic factors, including neurotrophin-4 (NT-4) and glial-cell-derived neurotrophic factor (GDNF), in OExo, which facilitated the iPSCs’ differentiation into DA neurons in an LIM homeobox transcription factor 1 alpha (LMX1A)-dependent manner. Our study provides novel insight into the biological properties of cerebral organoids and highlights the potential of OExo in the treatment of neurodegenerative diseases such as PD.
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spelling pubmed-103417362023-07-14 Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation Ji, Xingrui Zhou, Shaocong Wang, Nana Wang, Jingwen Wu, Yue Duan, Yuhan Ni, Penghao Zhang, Jingzhong Yu, Shuang Int J Mol Sci Article The remarkable advancements related to cerebral organoids have provided unprecedented opportunities to model human brain development and diseases. However, despite their potential significance in neurodegenerative diseases such as Parkinson’s disease (PD), the role of exosomes from cerebral organoids (OExo) has been largely unknown. In this study, we compared the effects of OExo to those of mesenchymal stem cell (MSC)-derived exosomes (CExo) and found that OExo shared similar neuroprotective effects to CExo. Our findings showed that OExo mitigated H(2)O(2)-induced oxidative stress and apoptosis in rat midbrain astrocytes by reducing excess ROS production, antioxidant depletion, lipid peroxidation, mitochondrial dysfunction, and the expression of pro-apoptotic genes. Notably, OExo demonstrated superiority over CExo in promoting the differentiation of human-induced pluripotent stem cells (iPSCs) into dopaminergic (DA) neurons. This was attributed to the higher abundance of neurotrophic factors, including neurotrophin-4 (NT-4) and glial-cell-derived neurotrophic factor (GDNF), in OExo, which facilitated the iPSCs’ differentiation into DA neurons in an LIM homeobox transcription factor 1 alpha (LMX1A)-dependent manner. Our study provides novel insight into the biological properties of cerebral organoids and highlights the potential of OExo in the treatment of neurodegenerative diseases such as PD. MDPI 2023-07-04 /pmc/articles/PMC10341736/ /pubmed/37446226 http://dx.doi.org/10.3390/ijms241311048 Text en © 2023 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
Ji, Xingrui
Zhou, Shaocong
Wang, Nana
Wang, Jingwen
Wu, Yue
Duan, Yuhan
Ni, Penghao
Zhang, Jingzhong
Yu, Shuang
Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title_full Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title_fullStr Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title_full_unstemmed Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title_short Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation
title_sort cerebral-organoid-derived exosomes alleviate oxidative stress and promote lmx1a-dependent dopaminergic differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341736/
https://www.ncbi.nlm.nih.gov/pubmed/37446226
http://dx.doi.org/10.3390/ijms241311048
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