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Journal articles on the topic 'Mouse Brain Organoids'

Author: Grafiati

Published: 6 July 2024

Last updated: 31 July 2025

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1

Roosen, Mieke, Chris Meulenbroeks, Phylicia Stathi, et al. "BIOL-11. PRECLINICAL MODELLING OF PEDIATRIC BRAIN TUMORS USING ORGANOID TECHNOLOGY." Neuro-Oncology 25, Supplement_1 (2023): i8. http://dx.doi.org/10.1093/neuonc/noad073.030.

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Abstract Molecular characterization has resulted in improved classification of pediatric brain tumors, leading to many novel (sub)types with distinct oncodriving events. To study tumor biology and to perform translational research on each of these tumors, preclinical models are essential. However, we are currently lacking sufficient models, especially in vitro, to represent each (sub)type and their heterogeneity. To generate large series of preclinical in vitro models for pediatric brain tumors, we are using organoid technology. Cells from patient samples and patient-derived xenograft samples

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Simsa, Robin, Theresa Rothenbücher, Hakan Gürbüz, et al. "Brain organoid formation on decellularized porcine brain ECM hydrogels." PLOS ONE 16, no. 1 (2021): e0245685. http://dx.doi.org/10.1371/journal.pone.0245685.

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Human brain tissue models such as cerebral organoids are essential tools for developmental and biomedical research. Current methods to generate cerebral organoids often utilize Matrigel as an external scaffold to provide structure and biologically relevant signals. Matrigel however is a nonspecific hydrogel of mouse tumor origin and does not represent the complexity of the brain protein environment. In this study, we investigated the application of a decellularized adult porcine brain extracellular matrix (B-ECM) which could be processed into a hydrogel (B-ECM hydrogel) to be used as a scaffol

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3

Zhai, Xin (Alice), Milagros Suarez Palacios, Zilu Huang, et al. "Abstract 3845: A matching panel of tumor organoids and patient derived orthotopic xenograft mouse models (PDOX) of high-grade gliomas in EGFP-based SCID mice." Cancer Research 85, no. 8_Supplement_1 (2025): 3845. https://doi.org/10.1158/1538-7445.am2025-3845.

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Background: High grade glioma, also known as glioblastoma multiform (GBM) a highly aggressive brain tumor, requires advanced systems to study tumor-stroma interactions. Paired in vitro and in vivo model systems such as 3D organoids and PDOX models derived from EGFP-SCID mice offered a unique opportunity to precisely and rapidly differentiation of mouse (EGFP positive) from human tumor cells, thereby facilitating the visualization and analysis of tumor/normal cell interactions in vitro and in vivo. Methods: EGFP-SCID mice received intra-cranial implantation of pediatric (n=6) and adult (n=6) GB

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Sukhinich, K. K., K. M. Shakirova, E. B. Dashinimaev, and M. A. Aleksandrova. "Development of 3D Cerebral Aggregates in the Brain Ventricles of Adult Mice." Russian Journal of Developmental Biology 52, no. 3 (2021): 164–75. http://dx.doi.org/10.1134/s1062360421030061.

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Abstract The cerebral organoids are three-dimensional cell cultures formed from brain-specific cell types arising from embryonic or pluripotent stem cells. Organoids provide an opportunity to study the early stages of brain development and diseases of the central nervous system. However, the modeling of organoids is associated with a number of unsolved problems. Organoid production techniques involve a complex cell culture process that requires special media, growth factors, and often the use of a bioreactor. Even under standardized conditions, structures of different morphology are formed: fr

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5

Bao, Zhongyuan, Kaiheng Fang, Zong Miao, et al. "Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice." Oxidative Medicine and Cellular Longevity 2021 (November 22, 2021): 1–16. http://dx.doi.org/10.1155/2021/6338722.

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Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal c

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Ferdaos, Nurfarhana, Sally Lowell, and John O. Mason. "Pax6 mutant cerebral organoids partially recapitulate phenotypes of Pax6 mutant mouse strains." PLOS ONE 17, no. 11 (2022): e0278147. http://dx.doi.org/10.1371/journal.pone.0278147.

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Cerebral organoids show great promise as tools to unravel the complex mechanisms by which the mammalian brain develops during embryogenesis. We generated mouse cerebral organoids harbouring constitutive or conditional mutations in Pax6, which encodes a transcription factor with multiple important roles in brain development. By comparing the phenotypes of mutant organoids with the well-described phenotypes of Pax6 mutant mouse embryos, we evaluated the extent to which cerebral organoids reproduce phenotypes previously described in vivo. Organoids lacking Pax6 showed multiple phenotypes associat

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García-Delgado, Ana Belén, Rafael Campos-Cuerva, Cristina Rosell-Valle, et al. "Brain Organoids to Evaluate Cellular Therapies." Animals 12, no. 22 (2022): 3150. http://dx.doi.org/10.3390/ani12223150.

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Animal models currently used to test the efficacy and safety of cell therapies, mainly murine models, have limitations as molecular, cellular, and physiological mechanisms are often inherently different between species, especially in the brain. Therefore, for clinical translation of cell-based medicinal products, the development of alternative models based on human neural cells may be crucial. We have developed an in vitro model of transplantation into human brain organoids to study the potential of neural stem cells as cell therapeutics and compared these data with standard xenograft studies

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Yakoub, Abraam M., and Mark Sadek. "Analysis of Synapses in Cerebral Organoids." Cell Transplantation 28, no. 9-10 (2019): 1173–82. http://dx.doi.org/10.1177/0963689718822811.

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Cerebral organoids are an emerging cutting-edge technology to model human brain development and neurodevelopmental disorders, for which mouse models exhibit significant limitations. In the human brain, synaptic connections define neural circuits, and synaptic deficits account for various neurodevelopmental disorders. Thus, harnessing the full power of cerebral organoids for human brain modeling requires the ability to visualize and analyze synapses in cerebral organoids. Previously, we devised an optimized method to generate human cerebral organoids, and showed that optimal organoids express m

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9

Estridge, R. Chris, Jennifer E. O’Neill, and Albert J. Keung. "Matrigel Tunes H9 Stem Cell-Derived Human Cerebral Organoid Development." Organoids 2, no. 4 (2023): 165–76. http://dx.doi.org/10.3390/organoids2040013.

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Human cerebral organoids are readily generated from human embryonic stem cells and human induced pluripotent stem cells and are useful in studying human neurodevelopment. Recent work with human cerebral organoids have explored the creation of different brain regions and the impacts of soluble and mechanical cues. Matrigel is a gelatinous, heterogenous mixture of extracellular matrix proteins, morphogens, and growth factors secreted by Engelbreth-Holm-Swarm mouse sarcoma cells. It is a core component of almost all cerebral organoid protocols, generally supporting neuroepithelial budding and tis

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Antonica, Francesco, Lucia Santomaso, Davide Pernici, et al. "MODL-22. Establishment of a novel system to specifically trace and ablate quiescent/slow cycling cells in high-grade glioma." Neuro-Oncology 24, Supplement_1 (2022): i173. http://dx.doi.org/10.1093/neuonc/noac079.645.

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Abstract Pediatric and adult high-grade gliomas are the most common malignant brain tumors, with poor prognosis due to recurrence and tumor infiltration after surgical removal and chemotherapy. Quiescent/slow cycling stem cells have been proposed to be one of the main players of tumor relapse but their involvement in in the infiltration remain unclear. Despite they have been described in mouse models or after transcriptional profiling of human tumor samples, their direct visualization, targeting and ablation remains a challenge. Here, we identified a population of malignant cells expressing Pr

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Antonica, F., L. Santomaso, G. Aiello, D. Pernici, E. Miele, and L. Tiberi. "OS13.3.A Establishment of a novel system to specifically trace and ablate quiescent/slow cycling cells in high-grade glioma." Neuro-Oncology 23, Supplement_2 (2021): ii16. http://dx.doi.org/10.1093/neuonc/noab180.051.

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Abstract BACKGROUND High-grade gliomas are the most common malignant brain tumors, with poor prognosis due to recurrence and tumor infiltration after surgical removal and chemotherapy. Quiescent/slow cycling stem cells have been proposed to be one of the main players of tumor relapse but their involvement in in the infiltration remain unclear. Despite they have been described in mouse models or after transcriptional profiling of human tumor samples, their direct visualization, targeting and ablation remains a challenge. MATERIAL AND METHODS Tumors were induced over-expressing oncogenic forms o

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Lee, Won Ji, Jeong Eon Lee, Yean Ju Hong, et al. "Generation of brain organoids from mouse ESCs via teratoma formation." Stem Cell Research 49 (December 2020): 102100. http://dx.doi.org/10.1016/j.scr.2020.102100.

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Golebiewska, Anna, Ann-Christin Hau, Anais Oudin, et al. "TMOD-08. PRIMARY AND RECURRENT GLIOMA PATIENT-DERIVED ORTHOTOPIC XENOGRAFTS (PDOX) REPRESENT RELEVANT PATIENT AVATARS FOR PRECISION MEDICINE." Neuro-Oncology 22, Supplement_2 (2020): ii229. http://dx.doi.org/10.1093/neuonc/noaa215.959.

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Abstract Patient-derived cancer models are essential tools for studying tumor biology and for preclinical interventions. Although numerous clinical cancer trials are being conducted, many fail due to inappropriate selection of compounds at the preclinical stage. Therefore, better preclinical models are crucial for predicting successful clinical impact. Orthotropic patient-derived xenograft (PDOX) models are of particular importance for brain cancers, as they allow to better recapitulate the brain tumor environment and the blood brain barrier. We created a large collection of PDOXs from primary

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Mariani, Alessandro, Davide Comolli, Roberto Fanelli, Gianluigi Forloni, and Massimiliano De Paola. "Neonicotinoid Pesticides Affect Developing Neurons in Experimental Mouse Models and in Human Induced Pluripotent Stem Cell (iPSC)-Derived Neural Cultures and Organoids." Cells 13, no. 15 (2024): 1295. http://dx.doi.org/10.3390/cells13151295.

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Neonicotinoids are synthetic, nicotine-derived insecticides used worldwide to protect crops and domestic animals from pest insects. The reported evidence shows that they are also able to interact with mammalian nicotine receptors (nAChRs), triggering detrimental responses in cultured neurons. Exposure to high neonicotinoid levels during the fetal period induces neurotoxicity in animal models. Considering the persistent exposure to these insecticides and the key role of nAChRs in brain development, their potential neurotoxicity on mammal central nervous system (CNS) needs further investigations

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Gebing, Philip, Stefanos Loizou, Sebastian Hänsch, et al. "CNS Invasion of TCF3::PBX1+ Leukemia Cells Requires Upregulation of AP-1 Signaling As Revealed By Brain Organoid Model." Blood 142, Supplement 1 (2023): 1407. http://dx.doi.org/10.1182/blood-2023-178613.

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Introduction: Involvement of the central nervous system (CNS) remains a challenge in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Currently, the investigation of CNS leukemia mechanisms relies heavily on 2D cell culture and mouse models. However, given the differences between human and murine CNS in cellular identity and architecture, it becomes crucial to explore alternative models to study CNS leukemia. Moreover, novel targets for diagnosis and treatment of CNS ALL are critically needed. Methods: In this study, we established a pioneering 3D co-culture model that combin

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Posadas, Inmaculada, Laura Romero-Castillo, Rosa-Anna Ronca, et al. "Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death." International Journal of Molecular Sciences 23, no. 8 (2022): 4391. http://dx.doi.org/10.3390/ijms23084391.

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Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D-aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotect

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17

Islam, Rehnuma, Humna Noman, Ashkan Azimi, et al. "Primitive and Definitive Neural Precursor Cells Are Present in Human Cerebral Organoids." International Journal of Molecular Sciences 25, no. 12 (2024): 6549. http://dx.doi.org/10.3390/ijms25126549.

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Activation of neural stem cells (NSCs) correlates with improved functional outcomes in mouse models of injury. In the murine brain, NSCs have been extensively characterized and comprise (1) primitive NSCs (pNSCs) and (2) definitive NSCs (dNSCs). pNSCs are the earliest cells in the NSC lineage giving rise to dNSCs in the embryonic and adult mouse brain. pNSCs are quiescent under baseline conditions and can be activated upon injury. Herein, we asked whether human pNSCs and dNSCs can be isolated during the maturation of human cerebral organoids (COs) and activated by drugs known to regulate mouse

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18

Yokoi, Remi, Nami Nagafuku, Yuto Ishibashi, Naoki Matsuda, and Ikuro Suzuki. "Contraindicated Drug Responses in Dravet Syndrome Brain Organoids Utilizing Micro Electrode Array Assessment Methods." Organoids 2, no. 4 (2023): 177–91. http://dx.doi.org/10.3390/organoids2040014.

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Ensuring drug safety for patients with specific neurological disorders is of paramount importance. For instance, certain antiepileptic drugs (AEDs) are contraindicated in Dravet Syndrome (DS), which is characterized by a deficiency in Na+ channel function. Constructing in vitro assessment methods capable of detecting contraindicated drug responses and medication effects on neurons derived from DS patients is highly anticipated for drug safety assessment and therapeutic innovation. This study used micro electrode array (MEA) measurements with low-frequency analysis on human iPSC-derived DS orga

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Ramirez, Santiago, Abhisek Mukherjee, Sofia Sepulveda, et al. "Modeling Traumatic Brain Injury in Human Cerebral Organoids." Cells 10, no. 10 (2021): 2683. http://dx.doi.org/10.3390/cells10102683.

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Traumatic brain injury (TBI) is a head injury that disrupts the normal brain structure and function. TBI has been extensively studied using various in vitro and in vivo models. Most of the studies have been done with rodent models, which may respond differently to TBI than human nerve cells. Taking advantage of the recent development of cerebral organoids (COs) derived from human induced pluripotent stem cells (iPSCs), which resemble the architecture of specific human brain regions, here, we adapted the controlled cortical impact (CCI) model to induce TBI in human COs as a novel in vitro platf

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20

Zhou, Qinjie, Diego F. Niño, Yukihiro Yamaguchi, et al. "Necrotizing enterocolitis induces T lymphocyte–mediated injury in the developing mammalian brain." Science Translational Medicine 13, no. 575 (2021): eaay6621. http://dx.doi.org/10.1126/scitranslmed.aay6621.

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Necrotizing enterocolitis (NEC) causes acute intestinal necrosis in premature infants and is associated with severe neurological impairment. In NEC, Toll-like receptor 4 is activated in the intestinal epithelium, and NEC-associated brain injury is characterized by microglial activation and white matter loss through mechanisms that remain unclear. We now show that the brains of mice and humans with NEC contained CD4+ T lymphocytes that were required for the development of brain injury. Inhibition of T lymphocyte influx into the brains of neonatal mice with NEC reduced inflammation and prevented

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Harding, Alfred T., Lee Gehrke, Jatin M. Vyas, and Hannah Brown Harding. "Human Brain Organoids: A New Model to Study Cryptococcus neoformans Neurotropism." Journal of Fungi 11, no. 7 (2025): 539. https://doi.org/10.3390/jof11070539.

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With the rise in immunocompromised individuals and patients with immune-related comorbidities such as COVID-19, the rate of fungal infections is growing. This increase, along with the current plateau in antifungal drug development, has made understanding the pathogenesis and dissemination of these organisms more pertinent than ever. The mouse model of fungal infection, while informative on a basic scientific level, has severe limitations in terms of translation to the human disease. Here we present data supporting the implementation of the human cerebral organoid model, which is generated from

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Ciarpella, Francesca, Raluca Georgiana Zamfir, Alessandra Campanelli, et al. "Generation of mouse hippocampal brain organoids from primary embryonic neural stem cells." STAR Protocols 4, no. 3 (2023): 102413. http://dx.doi.org/10.1016/j.xpro.2023.102413.

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Alaali, Lujain, Jinchong Xu, Jeff Mumm, Ming Yuan, Charles Eberhart, and Eric Raabe. "BIOL-13. DEPLOYING NEW MODELS OF NF-1 MUTANT LOW GRADE GLIOMA TO ACCELERATE THERAPEUTIC DEVELOPMENT." Neuro-Oncology 25, Supplement_1 (2023): i8. http://dx.doi.org/10.1093/neuonc/noad073.032.

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Abstract Pediatric low grade glioma (pLGG) research is hampered by a paucity of genetically accurate cell line models and xenografts. To address this need, we have developed and characterized multiple in vivo and organoid models. We used cell reprogramming conditions (CRC) to establish and propagate JHH-NF1-PA1, a NF1-mutant line derived from a low grade optic pathway glioma of a patient with type 1 neurofibromatosis. JHH-NF1-PA1 cells persist and take up midline positions when xenografted into the brains of zebrafish, allowing testing of therapeutics in vivo. We developed a human iPSC-brain o

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Song, Chenyun, Xinyu Chen, Jixin Ma, et al. "Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids." Journal of Tissue Engineering 14 (January 2023): 204173142211471. http://dx.doi.org/10.1177/20417314221147113.

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Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual

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Kan, Ryan, Weihong Ge, Can Yilgor, et al. "CSIG-15. PTN-PTPRZ1 SIGNALING MEDIATES TUMOR-NORMAL CROSSTALK IN GLIOBLASTOMA." Neuro-Oncology 25, Supplement_5 (2023): v43. http://dx.doi.org/10.1093/neuonc/noad179.0171.

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Abstract Glioblastoma (GBM) is the most devastating form of brain cancer with poor patient prognosis and high recurrence. An increasing body of literature suggests crosstalk between tumor and its surroundings, both molding the immune microenvironment and forming functional synapses with neighboring normal cells. Despite the high intra-tumoral and inter-patient heterogeneity, we have discovered PTN-PTPRZ1 signaling as the most significant and preserved communication pathway between GBM cells and their immediate neighboring cells. Through a novel tumor transplantation protocol onto cortical orga

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Tiberi, Luca. "PDTM-35. MODELLING MEDULLOBLASTOMA WITH MOUSE MODELS AND HUMAN CEREBELLAR ORGANOIDS." Neuro-Oncology 21, Supplement_6 (2019): vi195. http://dx.doi.org/10.1093/neuonc/noz175.811.

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Abstract Malignant medulloblastoma (MB) is the most common brain tumor affecting children and it remains responsible for a high percentage of morbidity and mortality among cancer patients. During the past few years, studies on human MB and mouse models have uncovered the existence of four major MB groups, with specific pathological and molecular features: WNT, SHH, Group 3 and Group 4. Of the four groups, patients with Group 3 MB have the worst outcome with nearly 50% of the tumors metastatic at the time of diagnosis. Therefore, developing “humanized “ mouse model of Group3 Medulloblastoma wou

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Slonchak, Andrii, Leon E. Hugo, Morgan Freney, et al. "Zika Virus sfRNA Plays an Essential Role in the Infection of Insects and Mammals." Proceedings 50, no. 1 (2020): 112. http://dx.doi.org/10.3390/proceedings2020050112.

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Similar to other flaviviruses, Zika virus (ZIKV) produces abundant subgenomic flavivirus RNA (sfRNA) derived from the 3’ untranslated region. The molecular mechanisms that determine the functions of sfRNA are currently not completely understood. Here, we created ZIKV mutants deficient in sfRNA production and employed them to investigate the role of this RNA in virus interactions with mammalian and insect hosts. We found that in mosquitoes, sfRNA facilitates virus replication and is required for ZIKV dissemination into saliva and virus transmission. The production of sfRNA was found to have no

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Gautam, Shailendra K., Ranjana K. Kanchan, Jawed A. Siddiqui, et al. "Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer." Cancers 12, no. 10 (2020): 2838. http://dx.doi.org/10.3390/cancers12102838.

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Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse mod

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Faisal, Syed M., Monika Yadav, Garrett R. Gibson, et al. "Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions." Cancers 17, no. 13 (2025): 2221. https://doi.org/10.3390/cancers17132221.

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Pediatric high-grade gliomas (pHGGs), particularly diffuse midline gliomas (DMGs), are among the most lethal brain tumors due to poor survival and resistance to therapies. DMGs possess a distinct genetic profile, primarily driven by hallmark mutations such as H3K27M, ACVR1, and PDGFRA mutations/amplifications and TP53 inactivation, all of which contribute to tumor biology and therapeutic resistance. Developing physiologically relevant preclinical models that replicate both tumor biology and the tumor microenvironment (TME) is critical for advancing effective treatments. This review highlights

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Drucker, Kristen, Thomas Kollmeyer, Connor Yanchus, et al. "MODL-03. IDH-MUTANT GLIOMA GWAS ALLELE RS55705857 ON 8Q24 IS CHANGING THE DYNAMICS OF UNPATTERNED CEREBRAL ORGANOID DEVELOPMENT." Neuro-Oncology 24, Supplement_7 (2022): vii291. http://dx.doi.org/10.1093/neuonc/noac209.1131.

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Abstract BACKGROUND The topologically associated domain (TAD) on 8q24 surrounding MYC is important for many types of cancer. The region is also important in the formation of IDH-mutant glioma; the risk allele rs55705857 being associated with the development of these tumors. The rs55705857 risk allele significantly increased the formation of tumors in an IDH-mutant mouse model. Cerebral organoids have been found to recapitulate the early development of the brain. We hypothesized that the rs55705857 risk allele may alter the phenotype of cerebral organoids. METHODS Isogenic induced pluripotent s

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Gamboa, Christian Moya, Kelly Jara, Sahithi Pamarthy, et al. "Generation of glioblastoma patient-derived organoids and mouse brain orthotopic xenografts for drug screening." STAR Protocols 2, no. 1 (2021): 100345. http://dx.doi.org/10.1016/j.xpro.2021.100345.

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Kishida, Kunihiro, Sarah C. Pearce, Shiyan Yu, Nan Gao, and Ronaldo P. Ferraris. "Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 312, no. 6 (2017): G592—G605. http://dx.doi.org/10.1152/ajpgi.00416.2016.

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Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts in

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Ge, Weihong, Ryan Kan, Elisa Fazzari, et al. "TMIC-05. UNVEILING THE IMPACT OF PTN-PTPRZ1 SIGNALING ON GLIOBLASTOMA PROGRESSION THROUGH TUMOR MICROENVIRONMENT COMMUNICATION." Neuro-Oncology 25, Supplement_5 (2023): v278—v279. http://dx.doi.org/10.1093/neuonc/noad179.1071.

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Abstract Glioblastoma (GBM) is the most lethal primary brain tumor with high rate of recurrence. GBM’s high inter- and intra-heterogeneity present a huge challenge to both disease modeling and treatment. Recent progress in the field has highlighted the role of signals associated with the microenvironment factor in driving tumor progression, suggesting that more detailed characterizations of the GBM microenvironment may provide novel therapeutic targets. In this study, we used a novel stem cell derived cortical organoid transplantation model, where we transplanted patient IDH wild type GBM cell

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Sun, Alfred Xuyang, Qiang Yuan, Masahiro Fukuda, et al. "Potassium channel dysfunction in human neuronal models of Angelman syndrome." Science 366, no. 6472 (2019): 1486–92. http://dx.doi.org/10.1126/science.aav5386.

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Disruptions in the ubiquitin protein ligase E3A (UBE3A) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as

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Cerrizuela, Santiago, Oguzhan Kaya, Lukas P. M. Kremer, et al. "High-throughput scNMT protocol for multiomics profiling of single cells from mouse brain and pancreatic organoids." STAR Protocols 3, no. 3 (2022): 101555. http://dx.doi.org/10.1016/j.xpro.2022.101555.

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Cui, Zeyu, Xin Liu, Xijin Gao, Zhihua Yu, Weidong Pan, and Te Liu. "Rotenone-driven DNA hypermethylation of the miR-6991–3p promoter induces death of mouse brain organoids." Tissue and Cell 95 (August 2025): 102831. https://doi.org/10.1016/j.tice.2025.102831.

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Nguyen, Phuong, Fadi Jacob, Ryan Salinas, Daniel Zhang, Hongjun Song, and Guo-li Ming. "TMOD-26. MODELING GLIOBLASTOMA BY IMPLANTATION OF INTACT PATIENT-DERIVED ORGANOIDS INTO RODENT BRAINS." Neuro-Oncology 21, Supplement_6 (2019): vi268. http://dx.doi.org/10.1093/neuonc/noz175.1125.

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Abstract Glioblastoma multiforme (GBM) is the most common primary and aggressive brain tumors in adults with extremely poor prognosis and limited treatment options. A major hallmark of GBM is the rapid and diffused infiltration of tumor cells into the surrounding healthy tissue that contribute to tumor recurrence and therapeutic resistance. However, existing in vitro cell culture or in vivo xenograft models inadequately recapitulate the inter-tumoral and intra-tumoral heterogeneity which are key features of GBM. For example, common oncogenic drivers of GBM such as epidermal growth factor recep

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Moreno-Sanchez, P. M., A. Oudin, Y. A. Yabo, et al. "OS10.5.A Modeling immunocompetent tumor microenvironment in glioblastoma patient-derived orthotopic xenografts." Neuro-Oncology 24, Supplement_2 (2022): ii21—ii22. http://dx.doi.org/10.1093/neuonc/noac174.068.

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Abstract Background To date, glioblastoma (GBM) remains a fatal disease, with a median overall survival of roughly over a year. There is a crucial need of new treatment options, yet most clinical trials have failed partly due to the lack of predictive preclinical model systems. Currently, most patient-derived preclinical models suffer from the reduction or absence of immune system components, which represents a bottleneck for adequate immunotherapy testing. Humanized mice offer new opportunities here, since they rebuild an adaptive human immune system in a NSG mouse. Derivation of glioblastoma

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Oten, Sena, Saritha Krishna, Thiebaud Picart, Andy Daniel, Cesar Nava Gonzales, and Katie Lu. "TMOD-28. MODELING MICROENVIRONMENTAL DYNAMICS: A NOVEL 3D GLIOMA-NEURON FUSION MODEL." Neuro-Oncology 26, Supplement_8 (2024): viii325. http://dx.doi.org/10.1093/neuonc/noae165.1292.

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Abstract Gliomas engage in bidirectional interactions with their microenvironment, wherein neuronal activity influences glioma proliferation and gliomas induce neuronal hyperexcitability. Although various models elucidate this complex interplay, a preference for a three-dimensional (3D) cell culture model has emerged to mimic intra-tumoral heterogeneity and microenvironmental interactions influencing glioma invasion, resistance, and recurrence. This study introduces an in vitro, self-assembled, scaffold-free, neuron-glioma spheroid fusion model to investigate the electrophysiological and funct

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Amado, Beatriz, Lúcia Melo, Raquel Pinto, Andrea Lobo, Pedro Barros, and João R. Gomes. "Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models." Biomedicines 10, no. 10 (2022): 2561. http://dx.doi.org/10.3390/biomedicines10102561.

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Ischemic stroke is a leading cause of death worldwide, mainly in western countries. So far, approved therapies rely on reperfusion of the affected brain area, by intravenous thrombolysis or mechanical thrombectomy. The last approach constitutes a breakthrough in the field, by extending the therapeutic window to 16–24 h after stroke onset and reducing stroke mortality. The combination of pharmacological brain-protective strategies with reperfusion is the future of stroke therapy, aiming to reduce brain cell death and decrease patients’ disabilities. Recently, a brain-protective drug—nerinetide—

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Mao, Rui, Xiaoyun Zhang, Youyong Kong, et al. "Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing." Cerebral Cortex 31, no. 8 (2021): 3911–24. http://dx.doi.org/10.1093/cercor/bhab058.

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Abstract Precise regulation of embryonic neurodevelopment is crucial for proper structural organization and functioning of the adult brain. The key molecular machinery orchestrating this process remains unclear. Anaplastic lymphoma kinase (ALK) is an oncogenic receptor-type protein tyrosine kinase that is specifically and transiently expressed in developing nervous system. However, its role in the mammalian brain development is unknown. We found that transient embryonic ALK inactivation caused long-lasting abnormalities in the adult mouse brain, including impaired neuronal connectivity and cog

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Collot, Raphael, Cristian Ruiz Moreno, Amber Wezenaar, et al. "DIPG-11. DISSECTING THE DIFFUSE MIDLINE GLIOMA TUMOR MICROENVIRONMENT COMMUNICATIONS USING MULTI-OMICS APPROACHES." Neuro-Oncology 25, Supplement_1 (2023): i15. http://dx.doi.org/10.1093/neuonc/noad073.058.

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Abstract Diffuse midline glioma (DMG) represents a highly aggressive pediatric brain tumor with no chance of survival. Treatment options are urgently needed, and efforts have been put towards developing T-cell immunotherapy. However, this should consider DMG’s unique tumor microenvironment (TME), both in terms of anatomical location and developmental stage. To gain knowledge on this unique tumor niche, we implemented an immuno-competent, syngeneic mouse model based on in-utero electroporation (IUE) of the key driver mutations to induce tumor formation at an embryonic stage. We characterized DM

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Antonica, Francesco, Francesca Garilli, Maria Del Mar Gardeazabal Bataller, Lucia Santomaso, and Luca Tiberi. "TMOD-06. MODELLING ADULT AND PAEDIATRIC GLIOBLASTOMA MULTIFORME (GBM) USING A GENE SCREEN-BASED APPROACH IN MICE AND HUMAN IPSC-DERIVED CEREBRAL ORGANOIDS." Neuro-Oncology 21, Supplement_6 (2019): vi263. http://dx.doi.org/10.1093/neuonc/noz175.1105.

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Abstract Glioblastoma multiforme (GBM) represent the most devastating form of high-grade glioma (HGG) affecting adults and children. Despite a multi-therapeutic approach consisting in surgery, radio- and chemo-therapy the prognosis remains poor. Several models such as xenograft, animal models and recently organoids, have been developed in order to investigate the physiopathology of GBM. Although several mouse models (where either gain- or loss-of function of genes/pathway found altered in patients induce tumour formation) have been generated many aspects of how the tumour is formed, evolves, i

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Cheng, Xiaoqing (Cathy), Khooshbu Kantibhai Patel, Yiwei Fu, et al. "Abstract 2634: IL34-induced Arg1 positive macrophage cells at the edge of invasion in cerebellum metastasis model of HER2-positive breast cancer." Cancer Research 85, no. 8_Supplement_1 (2025): 2634. https://doi.org/10.1158/1538-7445.am2025-2634.

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Abstract Brain metastases occur in about 30% breast cancer patients. The cerebellum is a frequent location for metastases in HER2-positive breast cancer patients, but the mechanisms for this is unknown. We hypothesize that the cerebellar microenvironment plays a crucial role in promoting the growth of metastatic HER2+ breast cancer cells. To study the interaction between cerebellar cells and metastatic breast cancer, we developed a syngeneic, immunocompetent mouse model for breast cancer brain metastasis, by stereotactically injecting mouse breast cancer organoids with HER2V777L; PIK3CAH1047R

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Wilson, Madison N., Martin Thunemann, Xin Liu, et al. "Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex." Nature Communications 13, no. 1 (2022). http://dx.doi.org/10.1038/s41467-022-35536-3.

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AbstractHuman cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, match

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Ma, Shaohua, Wanlong Wang, Jiaqi Zhou, et al. "Lamination-based organoid spatially resolved transcriptomics technique for primary lung and liver organoid characterization." Proceedings of the National Academy of Sciences 121, no. 46 (2024). http://dx.doi.org/10.1073/pnas.2408939121.

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Spatial-transcriptomics technologies have demonstrated exceptional performance in characterizing brain and visceral organ tissues, as well as brain and retinal organoids. However, it has not yet been proven whether spatial transcriptomics can effectively characterize primary tissue-derived organoids, as the standardized tissue sectioning or slicing methods are not applicable for such organoids. Herein, we present a technique, lamination-based organoid spatially resolved transcriptomics (LOSRT), for organoid-spatially resolved transcriptomics based on organoid lamination. Primary mouse lung and

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Dong, Xin, Shi-Bo Xu, Xin Chen, et al. "Human cerebral organoids establish subcortical projections in the mouse brain after transplantation." Molecular Psychiatry, October 13, 2020. http://dx.doi.org/10.1038/s41380-020-00910-4.

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Abstract Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids

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Aili, Yirizhati, Nuersimanguli Maimaitiming, Zengliang Wang, and Yongxin Wang. "Brain organoids: A new tool for modelling of neurodevelopmental disorders." Journal of Cellular and Molecular Medicine 28, no. 17 (2024). http://dx.doi.org/10.1111/jcmm.18560.

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AbstractNeurodevelopmental disorders are mostly studied using mice as models. However, the mouse brain lacks similar cell types and structures as those of the human brain. In recent years, emergence of three‐dimensional brain organoids derived from human embryonic stem cells or induced pluripotent stem cells allows for controlled monitoring and evaluation of early neurodevelopmental processes and has opened a window for studying various aspects of human brain development. However, such organoids lack original anatomical structure of the brain during maturation, and neurodevelopmental maturatio

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Xue, Jun, Youjun Chu, Yanwang Huang, et al. "A tumorigenicity evaluation platform for cell therapies based on brain organoids." Translational Neurodegeneration 13, no. 1 (2024). http://dx.doi.org/10.1186/s40035-024-00446-5.

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Abstract Background Tumorigenicity represents a critical challenge in stem cell-based therapies requiring rigorous monitoring. Conventional approaches for tumorigenicity evaluation are based on animal models and have numerous limitations. Brain organoids, which recapitulate the structural and functional complexity of the human brain, have been widely used in neuroscience research. However, the capacity of brain organoids for tumorigenicity evaluation needs to be further elucidated. Methods A cerebral organoid model produced from human pluripotent stem cells (hPSCs) was employed. Meanwhile, to

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Li, Yang, Peng-Ming Zeng, Jian Wu, and Zhen-Ge Luo. "Advances and Applications of Brain Organoids." Neuroscience Bulletin, May 24, 2023. http://dx.doi.org/10.1007/s12264-023-01065-2.

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AbstractUnderstanding the fundamental processes of human brain development and diseases is of great importance for our health. However, existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans. Over the past years, an emerging model, the “brain organoid” integrated from human pluripotent stem cells, has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent, making it possible to better understand the complex structures and functions of the human

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