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Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease
Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799361/ https://www.ncbi.nlm.nih.gov/pubmed/29402979 http://dx.doi.org/10.1038/s41598-018-20436-8 |
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author | Jorfi, Mehdi D’Avanzo, Carla Tanzi, Rudolph E. Kim, Doo Yeon Irimia, Daniel |
author_facet | Jorfi, Mehdi D’Avanzo, Carla Tanzi, Rudolph E. Kim, Doo Yeon Irimia, Daniel |
author_sort | Jorfi, Mehdi |
collection | PubMed |
description | Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time. We show that when suspended in three-dimensional extracellular matrix up to several weeks, the stem cell-derived neurospheroids display extensive neurite outgrowth and extend thick bundles of dendrites outward. We also cultivate genetically-engineered stem cell-derived neurospheroids with familial Alzheimer’s disease mutations for eight weeks in our microarray system. Interestingly, we observed robust accumulation of amyloid-β and phosphorylated tau, key hallmarks of Alzheimer’s disease. Overall, our in vitro model for engineering neurospheroid arrays is a valuable tool for studying complex neurodegenerative diseases and accelerating drug discovery. |
format | Online Article Text |
id | pubmed-5799361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57993612018-02-14 Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease Jorfi, Mehdi D’Avanzo, Carla Tanzi, Rudolph E. Kim, Doo Yeon Irimia, Daniel Sci Rep Article Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time. We show that when suspended in three-dimensional extracellular matrix up to several weeks, the stem cell-derived neurospheroids display extensive neurite outgrowth and extend thick bundles of dendrites outward. We also cultivate genetically-engineered stem cell-derived neurospheroids with familial Alzheimer’s disease mutations for eight weeks in our microarray system. Interestingly, we observed robust accumulation of amyloid-β and phosphorylated tau, key hallmarks of Alzheimer’s disease. Overall, our in vitro model for engineering neurospheroid arrays is a valuable tool for studying complex neurodegenerative diseases and accelerating drug discovery. Nature Publishing Group UK 2018-02-05 /pmc/articles/PMC5799361/ /pubmed/29402979 http://dx.doi.org/10.1038/s41598-018-20436-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jorfi, Mehdi D’Avanzo, Carla Tanzi, Rudolph E. Kim, Doo Yeon Irimia, Daniel Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title | Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title_full | Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title_fullStr | Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title_full_unstemmed | Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title_short | Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease |
title_sort | human neurospheroid arrays for in vitro studies of alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799361/ https://www.ncbi.nlm.nih.gov/pubmed/29402979 http://dx.doi.org/10.1038/s41598-018-20436-8 |
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