TY - INPR A1 - Schickel, Esther A1 - Bender, Tamara A1 - Kaysan, Leon A1 - Hufgard, Simone A1 - Mayer, Margot A1 - Grosshans, David R. A1 - Thielemann, Christiane A1 - Schroeder, Insa S. T1 - Human cerebral organoids model tumor infiltration and migration supported by astrocytes in an autologous setting T2 - bioRxiv N2 - SummaryEfforts to achieve precise and efficient tumor targeting of highly malignant brain tumors are constrained by the dearth of appropriate models to study the effects and potential side effects of radiation, chemotherapy, and immunotherapy on the most complex human organ, the brain. We established a cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC as one of the most common oncogenes in brain tumors. GFP+/c-MYChighcells were isolated from tumor organoids and used in two different culture approaches: assembloids comprising of a normal cerebral organoid with a GFP+/c-MYChightumor sphere and co-culture of cerebral organoid slices at air-liquid interface with GFP+/c-MYChighcells. GFP+/c-MYChighcells used in both approaches exhibited tumor-like properties, including overexpression of the c-MYC oncogene, high proliferative and invasive potential, and an immature phenotype as evidenced by increased expression of Ki-67, VIM, and CD133. Organoids and organoid slices served as suitable scaffolds for infiltrating tumor-like cells. Using our highly reproducible and powerful model system that allows long-term culture, we demonstrated that the migratory and infiltrative potential of tumor-like cells is shaped by the environment in which glia cells provide support to tumor-like cells. KW - Hirntumor Y1 - 2025 U6 - https://doi.org/https://doi.org/10.1101/2025.01.29.635456 VL - 2025 PB - Cold Spring Harbor Laboratory ER - TY - JOUR A1 - Schickel, Esther A1 - Bender, Tamara A1 - Kaysan, Leon A1 - Hufgard, Simone A1 - Mayer, Margot A1 - Grosshans, David R. A1 - Thielemann, Christiane A1 - Schroeder, Insa S. T1 - Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting JF - iScience N2 - Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior towards treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC, a common oncogene in brain tumors. GFP+/c-MYChigh cells were isolated from tumor organoids and used in two different approaches: GFP+/c-MYChigh cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids. GFP+/c-MYChigh cells used in both approaches exhibited tumor-like properties, including an immature phenotype and a highly proliferative and invasive potential. We demonstrate that the latter is influenced by astrocytes supporting the GFP+/c-MYChigh cells while X-ray irradiation significantly kills and impairs tissue infiltration of GFP+/c-MYChigh cells. In summary, the model represents major features of tumorous and adjacent normal tissue and may be used to evaluate appropriate cancer treatments. KW - Hirntumor Y1 - 2025 U6 - https://doi.org/https://doi.org/10.1016/j.isci.2025.113334 SN - 2589-0042 PB - Elsevier BV ER - TY - CHAP A1 - Hufgard, Simone A1 - Mayer, Margot A1 - Schroeder, Insa S. A1 - Thielemann, Christiane T1 - 3D compartmentilisation for analyzing functional long-range connectivity between brain regions T2 - 4th Microphysiological Systems World Summit, Brussels, Belgium KW - Hirnareal Y1 - 2025 IS - June 2025 ER -