Researchers at the University Hospital Bonn and the University of Bonn have developed Core2Edge, a human tissue-based model that mimics glioblastoma infiltration. By combining patient-derived tumor organoids with human brain slices, the model allows scientists to track single-cell invasion and study genetic heterogeneity using light-sheet microscopy and spatial transcriptomics. Published in Nature Protocols in 2026, Core2Edge offers a viable alternative to animal testing for drug screening.
Core2Edge glioblastoma tissue model
- ▪Researchers at the University Hospital Bonn and the University of Bonn developed Core2Edge, a model based entirely on human tissue that captures glioblastoma infiltration zones.
- ▪Core2Edge combines glioblastoma organoids grown from patient material with organotypic human brain-slice cultures prepared from routinely removed neurosurgical tissue.
- ▪The study detailing the Core2Edge model was published in the journal Nature Protocols in 2026.
Tumor infiltration beyond surgery
- ▪Glioblastoma cells migrate far beyond the visible tumor core into healthy brain tissue, making complete surgical removal impossible and causing tumor recurrence.
- ▪Core2Edge allows researchers to track tumor spread in human brain tissue from the tumor core to individual infiltrating tumor cells in distant brain regions.
Light-sheet fluorescence microscopy imaging
- ▪To improve light penetration and visibility of fine structures, the tissue is evenly expanded after fixation before scanning.
- ▪Researchers use high-resolution light-sheet fluorescence microscopy to create three-dimensional images of the entire tumor-infiltrated brain volume down to single-cell resolution.
Intratumoral heterogeneity in glioblastoma
- ▪Researchers applied spatial transcriptomics to show that the Core2Edge model recapitulates intratumoral heterogeneity, reflecting the genetic diversity found in patients.
- ▪Glioblastoma cells differ markedly in their genetic activity states even within a single tumor, a phenomenon known as intratumoral heterogeneity.
Therapy resistance mechanisms
- ▪Core2Edge lays the foundation for researching which cellular programs are active in infiltration zones to identify therapeutic targets that prevent tumor recurrence.
- ▪Intratumoral heterogeneity is considered a key driver of therapy resistance, allowing individual cell populations to survive radiation and chemotherapy and cause renewed tumor growth.
Human tissue alternative models
- ▪Because key aspects of glioblastoma biology can be studied directly in human tissue, Core2Edge offers an ethical and scientific alternative to animal models.
- ▪The Core2Edge model enables direct assessment of new drug candidates in human tissue without the need for animal testing.
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