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Silk scaffolding drives self-assembly of functional and mature human brain organoids

Sozzi, Edoardo LU orcid ; Kajtez, Janko LU orcid ; Bruzelius, Andreas LU ; Wesseler, Milan Finn ; Nilsson, Fredrik LU orcid ; Birtele, Marcella LU orcid ; Larsen, Niels B. ; Ottosson, Daniella Rylander LU orcid ; Storm, Petter LU orcid and Parmar, Malin LU orcid , et al. (2022) In Frontiers in Cell and Developmental Biology 10. p.1-17
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cerebral organoid, human pluripotent stem cells, oxygen sensing, silk scaffolding, tissue engineering
in
Frontiers in Cell and Developmental Biology
volume
10
article number
1023279
pages
1 - 17
publisher
Frontiers Media S. A.
external identifiers
  • pmid:36313550
  • scopus:85140839989
ISSN
2296-634X
DOI
10.3389/fcell.2022.1023279
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2022 Sozzi, Kajtez, Bruzelius, Wesseler, Nilsson, Birtele, Larsen, Ottosson, Storm, Parmar and Fiorenzano.
id
58bf5ecd-d9ab-4785-b9fd-0b3981baa010
date added to LUP
2022-12-06 16:21:41
date last changed
2024-11-15 14:18:19
@article{58bf5ecd-d9ab-4785-b9fd-0b3981baa010,
  abstract     = {{<p>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.</p>}},
  author       = {{Sozzi, Edoardo and Kajtez, Janko and Bruzelius, Andreas and Wesseler, Milan Finn and Nilsson, Fredrik and Birtele, Marcella and Larsen, Niels B. and Ottosson, Daniella Rylander and Storm, Petter and Parmar, Malin and Fiorenzano, Alessandro}},
  issn         = {{2296-634X}},
  keywords     = {{cerebral organoid; human pluripotent stem cells; oxygen sensing; silk scaffolding; tissue engineering}},
  language     = {{eng}},
  month        = {{10}},
  pages        = {{1--17}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cell and Developmental Biology}},
  title        = {{Silk scaffolding drives self-assembly of functional and mature human brain organoids}},
  url          = {{http://dx.doi.org/10.3389/fcell.2022.1023279}},
  doi          = {{10.3389/fcell.2022.1023279}},
  volume       = {{10}},
  year         = {{2022}},
}