Evidence map›Paper›PMID 41284925›Full record

ArticleNeuro-oncology2026

Development of a highly differentiated rat brain organoid model for exploring glioblastoma invasion dynamics and therapy.

Wenjing Zhou, Elena Martinez-Garcia, Katharina Sarnow, Georgia Kanli, Petr V Nazarov, Yaquan Li, Stephanie Gisela Schwab, Johannes Meiser, Christian Jaeger, Jakub Mieczkowski and 27 more

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Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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37 authors.

Wenjing ZhouDepartment of Blood Transfusion, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China (W.Z.).
Elena Martinez-GarciaProteomics of Cellular Signaling, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg, Luxembourg (E.M.-G., G.D.).
Katharina SarnowNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).ORCID 0000-0002-6091-5689
Georgia KanliTranslational Radiomics, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg (G.K., O.K.).
Petr V NazarovMultiomics Data Science Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg (P.V.N.).
Yaquan LiDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).
Stephanie Gisela SchwabNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Johannes MeiserCancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg (J.M.).
Christian JaegerLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg (C.J.).
Jakub Mieczkowski3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland (J.M., A.M.).
Agnieszka Misztak3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland (J.M., A.M.).
Frits A ThorsenNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Konrad GrützmannCore Unit for Molecular Tumour Diagnostics (CMTD), National Center for Tumour Diseases (NCT), Dresden, Germany (K.G., B.K.).ORCID 0000-0001-8942-0287
Boris MihaljevicDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway (B.M., B.V.L., M.B.).
Barbara Van LoonDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway (B.M., B.V.L., M.B.).ORCID 0000-0002-7597-207X
Jubayer A HossainNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Yan ZhangDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).
Zhiyi XueDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).
Wenjie LiDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).
Shannon S MoreinoNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Anna GolebiewskaNORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg (A.G., S.P.N., C.F.).ORCID 0000-0002-4160-2521
Simone P NiclouNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Magnar BjøråsDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway (B.M., B.V.L., M.B.).ORCID 0000-0001-8759-1170
Saverio TarditoCenter for Cancer Research, Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria (S.T.).
Justin V JoesphNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Taral R LunavatNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Halala S SaedNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Marzieh BahadorNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Mingzhi HanDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).ORCID 0000-0001-8357-5974
Carina FabianNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Hrvoje MileticNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Xingang LiDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).
Gunnar DittmarProteomics of Cellular Signaling, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg, Luxembourg (E.M.-G., G.D.).
Olivier KeunenTranslational Radiomics, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg (G.K., O.K.).
Barbara KlinkNORLUX Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway (W.Z., K.S., Y.L., S.G.S., F.A.T., J.A.H., S.S.M., S.P.N., J.V.J., T.R.L., H.S.S., M.B., M.H., C.F., H.M., B.K., J.W., R.B.).
Jian WangDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).ORCID 0000-0002-9482-5227
Rolf BjerkvigDepartment of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong, China (W.Z., Y.L., Y.Z., Z.X., W.L., M.H., X.L., J.W., R.B.).ORCID 0000-0002-9622-7263

Funding

Center for Cancer Research of the Medical University of ViennaFNR-ATTRACT A18/BM/11809970Luxembourg Research Fund PRIDE15/10675146National "111" Project B20058Natural Science Foundation of China 81972351Norwegian Cancer Society 208278Norwegian Cancer Society 220639Research Council of Norway 283790Research Council of Norway 287033Special Foundation for Taishan Scholars tshw201502056
6 · The paper itself

Abstract

backgroundHuman brain organoids (BOs) are important models for studying early brain development and neurological disorders. While techniques for creating BOs are advancing, they remain developmental structures. Therefore, when human BOs are used to studying glioma-host interactions, the tumor behavior may be influenced by the BO-developmental microenvironment. Here, we describe the maturation of rat brain organoids (rBOs) into fully differentiated BOs and demonstrate their value as a model for studying glioblastoma (GB)-host interactions and their use in testing therapeutic interventions. MATERIALS AND

methodsrBOs were obtained from fetal cortical brains on the 18th day of gestation. Transcriptomic, proteomic, and metabolomic analyses determined their differentiation into maturity. Their developmental trajectory was compared to human BOs derived from induced pluripotent stem cells as well as to rat brain development. Tumor-rBO interactions, including invasion parameters and therapeutic interactions, were studied using 5 human GB models.

resultsThe rBOs develop into organized structures with myelinated neurons, oligodendrocytes, synapses, and glial cells, mirroring the rat brain development. GB invasion in rBOs matched those observed in orthotopic xenografts, enabling real-time assessment of invasion metrics: cellular heterogeneity, single-cell invasion speed, and tumor progression. The BOs had a strong impact on GB transcriptional activity and can be used to study therapeutic interventions. The rBO differentiation status influenced GB invasion capacity.

conclusionsThe rBOs serve as an effective target brain structure for studying GB invasion parameters and for evaluating therapeutic interventions. Their rapid development into mature brain tissue makes rBOs a valuable brain avatar system for studying tumor-host interactions.

Indexed as

BrainBrain NeoplasmsCell DifferentiationGlioblastomaOrganoidsAnimalsDisease Models, AnimalHumansInduced Pluripotent Stem CellsNeoplasm InvasivenessRatsbrain microenvironmentbrain organoidsinvasiontherapy

Identifiers

PMID41284925
PMCPMC13070497

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