A refined protocol for the large-scale production of high-quality cerebral organoids

Simple item page
dc.contributor.authorProkhorova, Tatyana
dc.contributor.authorHohmann, Sonja Simone
dc.contributor.authorFabozzi, Alessia
dc.contributor.authorSaltarelli, Silvia
dc.contributor.authorAkimov, Vyacheslav
dc.contributor.authorYde Ohki, Cristine Marie
dc.contributor.authorMcNeill, Rhiannon V.
dc.contributor.authorTvedesøe, Christian
dc.contributor.authorBlagoev, Blagoy
dc.contributor.authorKittel-Schneider, Sarah
dc.contributor.authorSchneider-Kamp, Peter
dc.contributor.authorSmigielski, Lukasz
dc.contributor.authorQin, Jing
dc.contributor.authorDebrabant, Birgit
dc.contributor.authorGrünblatt, Edna
dc.contributor.authorMichel, Tanja Maria
dc.contributor.funderPUK Forschungsfonds Nr. 8702 “Fonds für wissenschaftliche Zwecke im Interesse der Heilung von psychiatrischen Krankheiten”
dc.contributor.funderUniversity Hospital of Frankfurt, Germany
dc.contributor.funderRegion Syddanmark
dc.contributor.funderNovo Nordisk Fonden, NNF, NNF22OC0080068
dc.contributor.funderDanmarks Frie Forskningsfond, DFF, DFF- 1026-00013B
dc.contributor.funderInterdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg, Z3-24
dc.contributor.funderMarie Sklodowska-Curie, 643051
dc.date.accessioned2026-07-13T13:50:05Z
dc.date.available2026-07-13T13:50:05Z
dc.date.issued2026-07-03
dc.description© 2026, the Author(s). 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material.
dc.description.abstractHuman pluripotent stem cell-derived cerebral organoids have emerged as a valuable tool for investigating early brain development and modeling neurodevelopmental disorders. However, considerable variation in both organoid size and cellular composition has been widely reported. Moreover, the large-scale production of organoids using conventional methods is a significant challenge, particularly considering that some stem cell lines exhibit variable efficiency in neuroepithelial formation. This heterogeneity of cerebral organoids can complicate experimental reproducibility and comparability in studies of brain development and disease mechanisms. Therefore, we developed a protocol using CERO 3D bioreactors, which enables scalable organoid production and improves size homogeneity compared to conventional approaches. In addition, we conducted a pilot study, utilizing MS-based proteomic analysis of single organoids from two different lines, aiming to explore whether size variability is associated with differences in protein expression within cerebral organoids. The organoids produced in the CERO 3D bioreactors reproducibly form neuroepithelial structures and express key neurodevelopmental markers. The presented protocol provides an efficient way of producing cerebral organoids, supporting reproducibility and high-throughput applications in neurodevelopmental research.en
dc.description.sponsorshipWe would like to express our gratitude to the patients and their families for their voluntary participation in the study and for providing their somatic cells. The study was funded by Strategic board of Psychiatry in the Region of Southern Denmark and the research funding agency of psychiatry in the region of Southern Denmark (psykiatrisk research fonden Region Syddanmark). JQ is supported by the Novo Nordic Recruit Grant 2024 (Project number -3310201). The proteomics work was partially funded by grants from the Novo Nordisk Foundation (NNF22OC0080068) and the Independent Research Fund Denmark (DFF- 1026-00013B). The iPSC lines obtained from the Swiss group were financially supported by the PUK Forschungsfonds Nr. 8702 “Fonds für wissenschaftliche Zwecke im Interesse der Heilung von psychiatrischen Krankheiten”. The SK55 and WLZ368 were generated within projects funded by IZKF Würzburg (Z3-24 to S.K.-S.), Marie Sklodowska-Curie grant agreement No 643051 and young researcher grant to SKS of the University Hospital of Frankfurt, Germany, respectively. We thank Dr. Mirolyuba Ilieva for the picture of organoids used in Fig. B, and OMNI Life Science for support with setting up the experimental workflow.
dc.format.extent13
dc.format.extent2131797
dc.identifier.authororcidProkhorova, Tatyana
dc.identifier.authororcidHohmann, Sonja Simone
dc.identifier.authororcidFabozzi, Alessia
dc.identifier.authororcidSaltarelli, Silvia
dc.identifier.authororcidAkimov, Vyacheslav
dc.identifier.authororcidYde Ohki, Cristine Marie§0000-0002-7414-2250
dc.identifier.authororcidMcNeill, Rhiannon V.
dc.identifier.authororcidTvedesøe, Christian
dc.identifier.authororcidBlagoev, Blagoy
dc.identifier.authororcidKittel-Schneider, Sarah
dc.identifier.authororcidSchneider-Kamp, Peter
dc.identifier.authororcidSmigielski, Lukasz
dc.identifier.authororcidQin, Jing
dc.identifier.authororcidDebrabant, Birgit
dc.identifier.authororcidGrünblatt, Edna
dc.identifier.authororcidMichel, Tanja Maria
dc.identifier.citationProkhorova, T, Hohmann, S S, Fabozzi, A, Saltarelli, S, Akimov, V, Yde Ohki, C M, McNeill, R V, Tvedesøe, C, Blagoev, B, Kittel-Schneider, S, Schneider-Kamp, P, Smigielski, L, Qin, J, Debrabant, B, Grünblatt, E & Michel, T M 2026, 'A refined protocol for the large-scale production of high-quality cerebral organoids', Journal of Neural Transmission, pp. 1--13. https://doi.org/10.1007/s00702-026-03216-x
dc.identifier.doi10.1007/s00702-026-03216-x
dc.identifier.endpage-13
dc.identifier.issn0300-9564
dc.identifier.journaltitleJournal of Neural Transmission
dc.identifier.otherORCID: /0000-0002-7414-2250/work/220588735
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19057
dc.identifier.urlhttps://www.scopus.com/pages/publications/105043725483
dc.language.isoeng
dc.rightscc_by
dc.subjectCerebral organoids
dc.subjectiPSCs
dc.subjectLarge-scale culture
dc.subjectNeuroepithelial formation
dc.subjectOrganoid heterogeneity
dc.subjectProteomics
dc.subject[APCMicrobiome]
dc.subject[Medicine]
dc.subjectNeurology
dc.subjectNeurology (clinical)
dc.subjectPsychiatry and Mental Health
dc.subjectBiological Psychiatry
dc.titleA refined protocol for the large-scale production of high-quality cerebral organoidsen
dc.typeArticle (Peer reviewed)
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s00702-026-03216-x.pdf
Size:
2.03 MB
Format:
Adobe Portable Document Format
Download
Collections
School of Medicine
APC Microbiome Ireland