Human tissue model tracks glioblastoma invasion cell by cell

by Inka Väth, University Hospital of Bonn

edited by Gaby Clark, reviewed by Robert Egan

Gaby Clark

Scientific Editor

Meet our editorial team
Behind our editorial process

Robert Egan

Senior Editor

Meet our editorial team
Behind our editorial process Editors' notes

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

proofread

The GIST Add as preferred source

Glioblastoma is a malignant brain tumor and is among the most aggressive cancers in humans. Despite multimodal therapy with surgery, radiation and chemotherapy, there is still no cure. A major reason is the tumor's invasive behavior: Glioblastoma cells migrate far beyond the visible tumor into healthy brain tissue. These infiltrating cells cannot be completely removed and seed tumor recurrence—often within just a few months.

"To understand why glioblastoma keeps coming back, we need to look closely at the tumor cells that remain hidden in the brain after surgery," says Dr. Matthias Schneider, deputy director of the Department of Neurosurgery at the UKB and head of the Brain Tumor Translational Research Group at the UKB and the University of Bonn. "Core2Edge allows us to study these infiltrative tumor cells in a model based entirely on human tissue, closely mirroring what we see in patients."

The study is published in the journal Nature Protocols.

Core2Edge combines glioblastoma organoids with human brain tissue in a single model

The research team from the Departments of Neurosurgery and Neuro-Oncology at the UKB combines glioblastoma organoids—miniature tumor tissues grown from freshly resected patient material—with organotypic human brain slice cultures. The slices are prepared from brain tissue that is routinely removed during neurosurgical procedures to access deeper target regions and would otherwise be discarded.

For Core2Edge, the organoids are implanted into the brain slices and co-cultured with the surrounding tissue. This allows tumor spread in human brain tissue to be tracked from the tumor core to individual infiltrating tumor cells, as they are found in brain regions distant from the solid tumor mass.

To visualize this process, the team uses high-resolution light-sheet fluorescence microscopy. After fixation, the tissue is first evenly expanded to improve light penetration and enhance the visibility of fine structures. The sample is then scanned layer by layer, creating three-dimensional images of the entire tumor-infiltrated brain volume—down to single-cell resolution.

"This allows us not only to quantify tumor cell spread in three dimensions, but also to trace morphology down to individual infiltrating cells," explains first author Ahmad Melhem, who co-developed the Core2Edge model as part of his doctoral research. "This approach provides a detailed view of the earliest steps of invasion and the spatial organization of tumor cells infiltrating the human brain."

In addition to high-resolution microscopy, the team also applied spatial transcriptomics. This technology reveals which genes are active in individual tumor cells and where exactly these cells are located in the tissue. This is particularly important in glioblastoma, as glioblastoma cells differ markedly in their genetic activity states even within a single tumor. This so-called intratumoral heterogeneity is considered a key driver of therapy resistance: Individual cell populations survive radiation and chemotherapy more effectively and give rise to renewed tumor growth.

"We were able to show that Core2Edge recapitulates intratumoral heterogeneity. This provides further evidence that the model closely reflects the situation in patients," says Dr. Anna-Laura Potthoff, a neurosurgeon and clinician-scientist at the Brain Tumor Translational Research Group. Core2Edge thus lays the foundation for future research into which cellular programs are active in the infiltration zones and which therapeutic targets may emerge to delay or prevent tumor recurrence.

Beyond its contribution to glioblastoma research, the model reduces reliance on animal experiments. "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," Schneider says.

Publication details

Ahmad Melhem et al, Core2Edge: a human glioblastoma organoid–brain slice model capturing infiltration and transcriptional heterogeneity from core to single-cell dispersion, Nature Protocols (2026). DOI: 10.1038/s41596-026-01412-3

Journal information: Nature Protocols

Key medical concepts

GlioblastomaSpatial Transcriptomics

Clinical categories

OncologyNeurology Provided by University Hospital of Bonn Who's behind this story?

Gaby Clark

MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

Citation: Human tissue model tracks glioblastoma invasion cell by cell (2026, July 28) retrieved 28 July 2026 from https://medicalxpress.com/news/2026-07-human-tissue-tracks-glioblastoma-invasion.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.