Towards a quality control framework for cerebral cortical organoids

Abstract Cerebral organoids offer significant potential for neuroscience research as complex in vitro models that mimic human brain development. However, challenges related to their quality and reproducibility hinder their reliability. Discrepancies in morphology, size, cellular composition, and cyt...

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Main Authors: Héloïse Castiglione, Lucie Madrange, Camille Baquerre, Benoît Guy Christian Maisonneuve, Thomas Lemonnier, Jean-Philippe Deslys, Frank Yates, Thibault Honegger, Jessica Rontard, Pierre-Antoine Vigneron
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14425-x
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author Héloïse Castiglione
Lucie Madrange
Camille Baquerre
Benoît Guy Christian Maisonneuve
Thomas Lemonnier
Jean-Philippe Deslys
Frank Yates
Thibault Honegger
Jessica Rontard
Pierre-Antoine Vigneron
author_facet Héloïse Castiglione
Lucie Madrange
Camille Baquerre
Benoît Guy Christian Maisonneuve
Thomas Lemonnier
Jean-Philippe Deslys
Frank Yates
Thibault Honegger
Jessica Rontard
Pierre-Antoine Vigneron
author_sort Héloïse Castiglione
collection DOAJ
description Abstract Cerebral organoids offer significant potential for neuroscience research as complex in vitro models that mimic human brain development. However, challenges related to their quality and reproducibility hinder their reliability. Discrepancies in morphology, size, cellular composition, and cytoarchitectural organization limit their applications, particularly in disease modeling, drug screening, and neurotoxicity testing. Critically, current methods for organoid characterization often lack standardization, restricting their broader applicability. To address the need for standardized quality assessment of cerebral organoids, we developed a Quality Control (QC) methodology for 60-day cortical organoids, evaluating five key criteria using a scoring system: morphology, size and growth profile, cellular composition, cytoarchitectural organization, and cytotoxicity. We implemented a hierarchical approach, beginning with non-invasive assessments to exclude low-quality organoids, while reserving in-depth analyses for those that passed the initial evaluation. To validate this framework, we exposed 60-day cortical organoids to graded doses of hydrogen peroxide (H2O2), inducing a range of quality outcomes. The QC system demonstrated its robustness by accurately discriminating organoid qualities. Our proposed QC framework is designed to be user-friendly, flexible, and broadly applicable, making it suitable for routine assessment of cerebral organoid quality. Additionally, its scalability enables industrial applications, offering a valuable tool for advancing both fundamental and pre-clinical research.
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spelling doaj-art-ae01854be7f44848bcce293ffe9c9d142025-08-20T03:42:49ZengNature PortfolioScientific Reports2045-23222025-08-0115111710.1038/s41598-025-14425-xTowards a quality control framework for cerebral cortical organoidsHéloïse Castiglione0Lucie Madrange1Camille Baquerre2Benoît Guy Christian Maisonneuve3Thomas Lemonnier4Jean-Philippe Deslys5Frank Yates6Thibault Honegger7Jessica Rontard8Pierre-Antoine Vigneron9SupBiotech, Ecole d’Ingénieurs en BiotechnologiesSupBiotech, Ecole d’Ingénieurs en BiotechnologiesNETRINETRISupBiotech, Ecole d’Ingénieurs en BiotechnologiesCommissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Service d’Etude des Prions et des Infections Atypiques (SEPIA), Université Paris-SaclaySupBiotech, Ecole d’Ingénieurs en BiotechnologiesNETRINETRISupBiotech, Ecole d’Ingénieurs en BiotechnologiesAbstract Cerebral organoids offer significant potential for neuroscience research as complex in vitro models that mimic human brain development. However, challenges related to their quality and reproducibility hinder their reliability. Discrepancies in morphology, size, cellular composition, and cytoarchitectural organization limit their applications, particularly in disease modeling, drug screening, and neurotoxicity testing. Critically, current methods for organoid characterization often lack standardization, restricting their broader applicability. To address the need for standardized quality assessment of cerebral organoids, we developed a Quality Control (QC) methodology for 60-day cortical organoids, evaluating five key criteria using a scoring system: morphology, size and growth profile, cellular composition, cytoarchitectural organization, and cytotoxicity. We implemented a hierarchical approach, beginning with non-invasive assessments to exclude low-quality organoids, while reserving in-depth analyses for those that passed the initial evaluation. To validate this framework, we exposed 60-day cortical organoids to graded doses of hydrogen peroxide (H2O2), inducing a range of quality outcomes. The QC system demonstrated its robustness by accurately discriminating organoid qualities. Our proposed QC framework is designed to be user-friendly, flexible, and broadly applicable, making it suitable for routine assessment of cerebral organoid quality. Additionally, its scalability enables industrial applications, offering a valuable tool for advancing both fundamental and pre-clinical research.https://doi.org/10.1038/s41598-025-14425-xCerebral organoidsQuality controlHierarchical scoring methodologyReproducibilityStandardization.
spellingShingle Héloïse Castiglione
Lucie Madrange
Camille Baquerre
Benoît Guy Christian Maisonneuve
Thomas Lemonnier
Jean-Philippe Deslys
Frank Yates
Thibault Honegger
Jessica Rontard
Pierre-Antoine Vigneron
Towards a quality control framework for cerebral cortical organoids
Scientific Reports
Cerebral organoids
Quality control
Hierarchical scoring methodology
Reproducibility
Standardization.
title Towards a quality control framework for cerebral cortical organoids
title_full Towards a quality control framework for cerebral cortical organoids
title_fullStr Towards a quality control framework for cerebral cortical organoids
title_full_unstemmed Towards a quality control framework for cerebral cortical organoids
title_short Towards a quality control framework for cerebral cortical organoids
title_sort towards a quality control framework for cerebral cortical organoids
topic Cerebral organoids
Quality control
Hierarchical scoring methodology
Reproducibility
Standardization.
url https://doi.org/10.1038/s41598-025-14425-x
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