@unpublished{Mayer2023, author = {Mayer, Margot}, title = {Aberrant choroid plexus formation in human cerebral organoids exposed to radiation}, doi = {https://doi.org/10.21203/rs.3.rs-3445801/v1}, pages = {22}, year = {2023}, abstract = {Brain tumor patients are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity, particularly the risk of radionecrosis. We used human cerebral organoids to investigate the mechanisms and nature of postirradiation brain image changes commonly linked to necrosis. Irradiation of cerebral organoids lead to increased formation of ZO1+/AQP1+/CLN3+-choroid plexus (CP) structures. Increased CP formation was triggered by radiation via the NOTCH/WNT signaling pathways and associated with delayed growth and neural stem cell differentiation, but not necrosis. The effect was more pronounced in immature than in mature organoids, reflecting the clinically-observed increased radiosensitivity of the pediatric brain. Protons were more effective than X-rays at the same dose, as also observed in clinical treatments. We conclude that radiation-induced brain image-changes can be attributed to aberrant CP formation, providing a new cellular mechanism and strategy for possible countermeasures.}, subject = {Hirntumor}, language = {en} } @techreport{MayerArrizabalagaRitteretal.2015, author = {Mayer, Margot and Arrizabalaga, Onetsine and Ritter, Sylvia and Thielemann, Christiane}, title = {Human embryonic stem cell derived neurospheres form functional networks on microelectrode arrays}, series = {GSI Scientific Report 2015}, volume = {2015}, journal = {GSI Scientific Report 2015}, number = {GSI Report 2016-1}, doi = {10.15120/GR-2016-1}, pages = {205 -- 205}, year = {2015}, subject = {Embryonale Stammzelle}, language = {en} } @unpublished{SchickelBenderKaysanetal.2025, author = {Schickel, Esther and Bender, Tamara and Kaysan, Leon and Hufgard, Simone and Mayer, Margot and Grosshans, David R. and Thielemann, Christiane and Schroeder, Insa S.}, title = {Human cerebral organoids model tumor infiltration and migration supported by astrocytes in an autologous setting}, series = {bioRxiv}, volume = {2025}, journal = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, doi = {https://doi.org/10.1101/2025.01.29.635456}, pages = {43}, year = {2025}, abstract = {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.}, subject = {Hirntumor}, language = {en} } @article{SchickelBenderKaysanetal.2025, author = {Schickel, Esther and Bender, Tamara and Kaysan, Leon and Hufgard, Simone and Mayer, Margot and Grosshans, David R. and Thielemann, Christiane and Schroeder, Insa S.}, title = {Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting}, series = {iScience}, journal = {iScience}, publisher = {Elsevier BV}, issn = {2589-0042}, doi = {https://doi.org/10.1016/j.isci.2025.113334}, year = {2025}, abstract = {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.}, subject = {Hirntumor}, language = {en} } @inproceedings{HufgardMayerSchroederetal.2025, author = {Hufgard, Simone and Mayer, Margot and Schroeder, Insa S. and Thielemann, Christiane}, title = {3D compartmentilisation for analyzing functional long-range connectivity between brain regions}, series = {4th Microphysiological Systems World Summit, Brussels, Belgium}, booktitle = {4th Microphysiological Systems World Summit, Brussels, Belgium}, number = {June 2025}, year = {2025}, subject = {Hirnareal}, language = {en} } @article{FlachsEtzelMayeretal.2022, author = {Flachs, Dennis and Etzel, Johannes and Mayer, Margot and Harbecke, Frederic and Belle, Stefan and Rickmeyer, Tim and Thielemann, Christiane}, title = {Characterization of electrically conductive, printable ink based on alginate hydrogel and graphene nanoplatelets}, series = {Biomedical Engineering Advances}, volume = {2022}, journal = {Biomedical Engineering Advances}, number = {4}, doi = {https://doi.org/10.1016/j.bea.2022.100045}, pages = {1 -- 2}, year = {2022}, abstract = {In recent years, there has been an increasing interest in electrically conductive hydrogels for a wide range of biomedical applications, like tissue engineering or biosensors. In this study, we present a cost-effective conductive hydrogel based on alginate and graphene nanoplatelets for extrusion-based bioprinters. The hydrogel is prepared under ambient conditions avoiding high temperatures detrimental for cell culture environments. Investigation of the hydrogel revealed a conductivity of up to 7.5 S/cm, depending on the ratio of platelets. Furthermore, in vitro tests with human embyronic kidney cells - as an example cell type - showed good adhesion of the cells to the surface of the conductive hydrogel. Electrochemical measurements revealed a low electrode impedance which is desirable for the extracellular recording, but also low electrode capacitance, which is unfavorable for electrical stimulation purposes. Therefore, future experiments with the graphene nanoplatelets-based hydrogels will focus on electrodes for biosensors and extracellular recordings of neurons or cardiac myocytes.}, subject = {Hydrogel}, language = {en} }