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Silk scaffolding drives self-assembly of functional and mature human brain organoids
Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brai...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614032/ https://www.ncbi.nlm.nih.gov/pubmed/36313550 http://dx.doi.org/10.3389/fcell.2022.1023279 |
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author | Sozzi, Edoardo Kajtez, Janko Bruzelius, Andreas Wesseler, Milan Finn Nilsson, Fredrik Birtele, Marcella Larsen, Niels B. Ottosson, Daniella Rylander Storm, Petter Parmar, Malin Fiorenzano, Alessandro |
author_facet | Sozzi, Edoardo Kajtez, Janko Bruzelius, Andreas Wesseler, Milan Finn Nilsson, Fredrik Birtele, Marcella Larsen, Niels B. Ottosson, Daniella Rylander Storm, Petter Parmar, Malin Fiorenzano, Alessandro |
author_sort | Sozzi, Edoardo |
collection | PubMed |
description | Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra-organoid variability, limiting their use in recapitulating later developmental stages as well as in disease modeling and drug discovery. In addition, cell stress and hypoxia resulting from long-term culture lead to incomplete maturation and cell death within the inner core. Here, we used a recombinant silk microfiber network as a scaffold to drive hPSCs to self-arrange into engineered cerebral organoids. Silk scaffolding promoted neuroectoderm formation and reduced heterogeneity of cellular organization within individual organoids. Bulk and single cell transcriptomics confirmed that silk cerebral organoids display more homogeneous and functionally mature neuronal properties than organoids grown in the absence of silk scaffold. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. The silk scaffolding strategy appears to reduce intra-organoid variability and enhances self-organization into functionally mature human brain organoids. |
format | Online Article Text |
id | pubmed-9614032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96140322022-10-29 Silk scaffolding drives self-assembly of functional and mature human brain organoids Sozzi, Edoardo Kajtez, Janko Bruzelius, Andreas Wesseler, Milan Finn Nilsson, Fredrik Birtele, Marcella Larsen, Niels B. Ottosson, Daniella Rylander Storm, Petter Parmar, Malin Fiorenzano, Alessandro Front Cell Dev Biol Cell and Developmental Biology Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra-organoid variability, limiting their use in recapitulating later developmental stages as well as in disease modeling and drug discovery. In addition, cell stress and hypoxia resulting from long-term culture lead to incomplete maturation and cell death within the inner core. Here, we used a recombinant silk microfiber network as a scaffold to drive hPSCs to self-arrange into engineered cerebral organoids. Silk scaffolding promoted neuroectoderm formation and reduced heterogeneity of cellular organization within individual organoids. Bulk and single cell transcriptomics confirmed that silk cerebral organoids display more homogeneous and functionally mature neuronal properties than organoids grown in the absence of silk scaffold. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. The silk scaffolding strategy appears to reduce intra-organoid variability and enhances self-organization into functionally mature human brain organoids. Frontiers Media S.A. 2022-10-14 /pmc/articles/PMC9614032/ /pubmed/36313550 http://dx.doi.org/10.3389/fcell.2022.1023279 Text en Copyright © 2022 Sozzi, Kajtez, Bruzelius, Wesseler, Nilsson, Birtele, Larsen, Ottosson, Storm, Parmar and Fiorenzano. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Sozzi, Edoardo Kajtez, Janko Bruzelius, Andreas Wesseler, Milan Finn Nilsson, Fredrik Birtele, Marcella Larsen, Niels B. Ottosson, Daniella Rylander Storm, Petter Parmar, Malin Fiorenzano, Alessandro Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title | Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title_full | Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title_fullStr | Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title_full_unstemmed | Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title_short | Silk scaffolding drives self-assembly of functional and mature human brain organoids |
title_sort | silk scaffolding drives self-assembly of functional and mature human brain organoids |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614032/ https://www.ncbi.nlm.nih.gov/pubmed/36313550 http://dx.doi.org/10.3389/fcell.2022.1023279 |
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