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Human cerebral organoids with microglia and vasculature model glioma stem cell interactions and radiotherapy response.

Overview

Authors: Jérémy Raguin1,2, Noa Legrand1,2, Thierry Kortulewski1,2, Oriane Bergiers1,2, Christine Granotier-Beckers1,2, Laure Chatrousse3, Alexandra Benchoua3, Laurent R. Gauthier1,2, François D. Boussin1,2, Marc-André Mouthon1,2
  1. Université Paris Cité, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, LRP/iRCM/IBFJ, 92265 Fontenay-aux-Roses, France
  2. Université Paris-Saclay, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, LRP/iRCM/IBFJ, 92265 Fontenay-aux-Roses, France
  3. IStem, CECS, AFM, Neuroplasticity and Therapeutics, 91100 Corbeil-Essonne, France
Journal: Cell reports methods, volume 6, issue 6, article 101425
Dates: received 12 May 2025; accepted 2 April 2026; published online 5 May 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.crmeth.2026.101425 · PMID 42092360 · PMCID PMC13282650 · OpenAlex W7160294713
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: iPSC, cerebral organoids, microglia, vascularized, endothelial cells, glioma, radiotherapy, glioblastoma, brain cancer, precision medicine
MeSH: Brain Neoplasms*, Cell Communication*, Glioma*, Microglia*, Neoplastic Stem Cells*, Organoids*, Animals, Brain, Coculture Techniques, Humans, Induced Pluripotent Stem Cells, Mice (* major topic)
Topic: Glioma Diagnosis and Treatment (Genetics, Medicine), according to OpenAlex
Citations: cited by 1 paper (Europe PMC); 62 references in the paper
Research resources: GFP RRID:AB_10001164, S100β RRID:AB_10013383, GFP RRID:AB_10128178, CD144-APC RRID:AB_10639861, Rabbit anti-Chicken-FITC RRID:AB_1075130, LAMININ a4 RRID:AB_10807830, CD11b-BV421 RRID:AB_10897942, Doublecortin (DCX) RRID:AB_11019667, CX3CR1-APC RRID:AB_11149136, Donkey anti-Mouse-AF488 RRID:AB_141607, Donkey anti-Rabbit-AF594 RRID:AB_141637, Donkey anti-Goat-AF647 RRID:AB_141844, PDGFRβ RRID:AB_2162633, SOX9 RRID:AB_2239761, SOX2 RRID:AB_2286686, PSD95 RRID:AB_2292883, GFAP RRID:AB_2294571, β3-tubulin RRID:AB_2313773, ZO-1 RRID:AB_2533147, Chicken anti-Mouse-AF488 RRID:AB_2535786, Donkey anti-Mouse-AF594 RRID:AB_2535789, Donkey anti-Rabbit-AF488 RRID:AB_2535792, Donkey anti-Goat-AF594 RRID:AB_2535871, CD45-APC RRID:AB_2562049, CD45-PE RRID:AB_2562057, CD31-BV605 RRID:AB_2562148, CD43-PE-Cy7 RRID:AB_2563698, CD31 RRID:AB_2566676, CD206-APC RRID:AB_2573182, CD49d-APC-Cy7 RRID:AB_2616848, CD163-BV510 RRID:AB_2650631, P2RY12 RRID:AB_2669027, HLADR-SB780 RRID:AB_2724457, CD11b-BB700 RRID:AB_2744272, Donkey anti-Mouse-AFplus647 RRID:AB_2762830, Donkey anti-Rabbit-AFplus647 RRID:AB_2762835, Donkey anti-Goat-AFplus488 RRID:AB_2762838, CD146-BV605 RRID:AB_2783271, P2RY12-BV421 RRID:AB_2783290, CD309-BV421 RRID:AB_2832739, OmniMap anti-Ms HRP RRID:AB_2885182, Connexin 43 RRID:AB_297976, Collagen IV RRID:AB_305584, AIF-1/Iba1 RRID:AB_3073939, CD31 RRID:AB_314328, SSEA3-AF488 RRID:AB_3646484, TRA-1-81-AF594 RRID:AB_3662726, CD31-PE RRID:AB_3662732, AIF-1/Iba1 RRID:AB_521594, GFAP RRID:AB_561049, MAP2 RRID:AB_94856, GM25256∗G RRID:CVCL_Y803, RRID:IMSR_JAX:005557, GraphPad Prism RRID:SCR_002798, IMARIS RRID:SCR_007370, FlowJo RRID:SCR_008520, Leica Application Suite X RRID:SCR_013673, StepOne RRID:SCR_014281, Leica SP8 LIGHTNING confocal microscope RRID:SCR_018169, BD FACSAria II Cell Sorter RRID:SCR_018934, Leica VT1200S vibrating microtome RRID:SCR_020243, RRID:SCR_023455, RRID:SCR_025506

Abstract

Most human brain organoid models derived from induced pluripotent stem cells (iPSCs) lack vascular and/or immune components, despite their critical roles in maintaining brain homeostasis and contributing to pathophysiological processes. We established a method for generating vascularized complex cerebral organoids (CCOs) containing microglial cells (brain-resident macrophages) by incorporating bipotent hematopoietic/endothelial progenitors derived from the same iPSC lines. This approach led to the formation of extensive vascular-like structures with blood-brain barrier characteristics, which were perfused upon transplantation into immunodeficient mice. Additionally, microglial cells exhibiting typical phenotypes also developed within the CCOs. By co-culturing CCOs with glioma stem cells, we demonstrated that this model recapitulates the tumor niche of glioblastoma, showing vascular co-option, reprogramming of microglia into tumor-associated macrophages, and recurrence after radiotherapy. In conclusion, our vascularized, immunocompetent CCO model provides a platform to study brain development, glioma pathogenesis, and therapies.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

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Data and code availability

• All data reported in this paper will be shared by the lead contact upon request. • This study does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 10 keywords, 12 MeSH terms, 5 funders, 62 references, 63 RRIDs.

Cite

This paper

Raguin, J., Legrand, N., Kortulewski, T., Bergiers, O., Granotier-Beckers, C., Chatrousse, L., Benchoua, A., Gauthier, L. R., Boussin, F. D., & Mouthon, M.-A. (2026). Human cerebral organoids with microglia and vasculature model glioma stem cell interactions and radiotherapy response. Cell reports methods, 6(6), 101425. https://doi.org/10.1016/j.crmeth.2026.101425

BibTeX

@article{raguin2026human,
author = {Raguin, Jérémy and Legrand, Noa and Kortulewski, Thierry and Bergiers, Oriane and Granotier-Beckers, Christine and Chatrousse, Laure and Benchoua, Alexandra and Gauthier, Laurent R. and Boussin, François D. and Mouthon, Marc-André},
title = {{Human cerebral organoids with microglia and vasculature model glioma stem cell interactions and radiotherapy response}},
journal = {Cell reports methods},
year = {2026},
month = may,
volume = {6},
number = {6},
pages = {101425},
publisher = {Elsevier},
issn = {2667-2375},
doi = {10.1016/j.crmeth.2026.101425},
url = {https://doi.org/10.1016/j.crmeth.2026.101425},
pmid = {42092360},
pmcid = {PMC13282650}
}

RIS

TY - JOUR
AU - Raguin, Jérémy
AU - Legrand, Noa
AU - Kortulewski, Thierry
AU - Bergiers, Oriane
AU - Granotier-Beckers, Christine
AU - Chatrousse, Laure
AU - Benchoua, Alexandra
AU - Gauthier, Laurent R.
AU - Boussin, François D.
AU - Mouthon, Marc-André
TI - Human cerebral organoids with microglia and vasculature model glioma stem cell interactions and radiotherapy response
T2 - Cell reports methods
J2 - Cell Rep Methods
PY - 2026
DA - 2026/05/05
VL - 6
IS - 6
SP - 101425
SN - 2667-2375
PB - Elsevier
DO - 10.1016/j.crmeth.2026.101425
UR - https://doi.org/10.1016/j.crmeth.2026.101425
LA - en
ER -

CSL-JSON

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