Researchers at the University Hospital Bonn and the University of Bonn announced on July 28 that they have developed Core2Edge, a new model based entirely on human tissue to study glioblastoma, an aggressive brain tumor known for its deep infiltration into surrounding brain tissue. The Core2Edge model captures hard-to-access infiltration zones at the tumor margin and enables direct assessment of new drug candidates in human tissue without animal testing.
Glioblastoma is considered one of the most aggressive cancers in humans. Despite multimodal therapy including surgery, radiation, and chemotherapy, there is currently no cure due to the tumor's invasive behavior. Tumor cells migrate far beyond visible boundaries into healthy brain tissue, making complete removal impossible and often leading to recurrence within months.
The research team from the Departments of Neurosurgery and Neuro-Oncology combined glioblastoma organoids—miniature tumors grown from freshly resected patient material—with organotypic human brain-slice cultures prepared from tissue routinely removed during neurosurgical procedures. In this approach, organoids are implanted into these slices and co-cultured with surrounding tissue. This allows tracking of tumor spread in human brain tissue from the core out to individual infiltrating cells located distant from the main tumor mass.
High-resolution light-sheet fluorescence microscopy was used to visualize this process by scanning fixed samples layer by layer, creating three-dimensional images down to single-cell resolution. "This allows us not only to quantify tumor cell spread in three dimensions, but also trace morphology down to individual infiltrating cells," said first author Ahmad Melhem. "This approach provides a detailed view of the earliest steps of invasion and the spatial organization of tumor cells infiltrating the human brain." Spatial transcriptomics was also applied to reveal which genes are active in individual tumor cells and their precise locations within tissues.
Dr. Anna-Laura Potthoff said, "We were able to show that Core2Edge recapitulates intratumoral heterogeneity. This provides further evidence that the model closely reflects the situation in patients." The researchers say this lays groundwork for future studies into cellular programs active in infiltration zones as well as potential therapeutic targets for delaying or preventing recurrence.
Schneider said, "As key aspects of glioblastoma biology—especially infiltration and intratumoral heterogeneity—can be studied directly in human tissue, Core2Edge offers a scientifically and ethically compelling alternative to animal models." The study involved collaboration among multiple departments at University Hospital Bonn as well as other institutes affiliated with University of Bonn.
