TY - JOUR
KW - glioblastoma
KW - invasiveness
KW - organoid fabrication
KW - tumor extracellular matrix
KW - tumor-host interactions
AU - Chao Liang
AU - Henry Robert Howard
AU - Shihui Chen
AU - Won-Young Choi
AU - Summer Cao
AU - Arthur Chien
AU - Kevin Zou
AU - Michael Kassiou
AU - Fabien Delerue
AU - Ho Sang Jung
AU - Yeonju Park
AU - Young Mee Jung
AU - Yong-Dae Kwon
AU - Karrie M. Kiang
AU - Gilberto Ka-Kit Leung
AU - Ryohichi Sugimura
AU - Ann-Na Cho
AU - Sang Jin Lee
AB - Glioblastoma (GBM) remains one of the most aggressive brain malignancies, characterized by rapid infiltration, therapeutic resistance, and dismal prognosis. Modeling GBM invasion in physiologically relevant systems has been hindered by the lack of reproducible platforms. Here, we present a bioengineered assembloid (ASM) system that integrates GBM cells encapsulated in self-degradable 5% oxidized alginate microgel (5OA) with dorsal forebrain organoids (DOs) to recapitulate early tumor-host interactions during glioblastoma invasion toward the brain. Live-cell imaging revealed GBM self-aggregation, leading to increased recruitment and invasion at the DO boundary, accompanied by strong cell-cell adhesion, nuclear compaction, and the infiltration fronts enriched in SOX2+/Vimentin+ tumor populations. Transcriptomic profiling demonstrated upregulation of adhesion, integrin clustering, and mechanosensing-associated genes, alongside downregulation of neuronal differentiation pathways, indicating a dual invasion and host suppression strategy. Comparative analyses of GBM-only constructs and DO-GBM ASMs revealed elevated expression of laminin subunits and enrichment of invasion-associated pathways, including PI3K-AKT-mTOR and TGF-β signaling, reflecting a shift toward an invasive state at the transcriptomic level. In vivo implantation of ASMs confirmed aggressive GBM infiltration and niche remodeling, highlighting the translational relevance. These findings suggest that it recapitulates the structural, molecular, and functional hallmarks of GBM invasion and tumor-driven remodeling of the host brain microenvironment.
BT - Advanced Healthcare Materials
DA - 2026
DO - 10.1002/adhm.202504842
IS - 33
LA - en
N2 - Glioblastoma (GBM) remains one of the most aggressive brain malignancies, characterized by rapid infiltration, therapeutic resistance, and dismal prognosis. Modeling GBM invasion in physiologically relevant systems has been hindered by the lack of reproducible platforms. Here, we present a bioengineered assembloid (ASM) system that integrates GBM cells encapsulated in self-degradable 5% oxidized alginate microgel (5OA) with dorsal forebrain organoids (DOs) to recapitulate early tumor-host interactions during glioblastoma invasion toward the brain. Live-cell imaging revealed GBM self-aggregation, leading to increased recruitment and invasion at the DO boundary, accompanied by strong cell-cell adhesion, nuclear compaction, and the infiltration fronts enriched in SOX2+/Vimentin+ tumor populations. Transcriptomic profiling demonstrated upregulation of adhesion, integrin clustering, and mechanosensing-associated genes, alongside downregulation of neuronal differentiation pathways, indicating a dual invasion and host suppression strategy. Comparative analyses of GBM-only constructs and DO-GBM ASMs revealed elevated expression of laminin subunits and enrichment of invasion-associated pathways, including PI3K-AKT-mTOR and TGF-β signaling, reflecting a shift toward an invasive state at the transcriptomic level. In vivo implantation of ASMs confirmed aggressive GBM infiltration and niche remodeling, highlighting the translational relevance. These findings suggest that it recapitulates the structural, molecular, and functional hallmarks of GBM invasion and tumor-driven remodeling of the host brain microenvironment.
PY - 2026
EP - e04842
ST - Flash Assembloids
T2 - Advanced Healthcare Materials
TI - Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma–Brain Organoid Interfaces
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202504842
VL - 15
Y2 - 2026-09-14
SN - 2192-2659
ER -