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Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix.

Overview

Authors: Autumn McManis1,2,3, Charles Ashley Jimenez2, Abha Shirolkar2, Syed Raza ur Rehman3, Sumana Mallick2,3, Malea Murphy4, Akhilesh K. Gaharwar1,3,5, Irtisha Singh1,2,3
  1. Interdisciplinary Graduate Program in Genetics and Genomics Texas A&M University College Station Texas USA
  2. Department of Cell Biology and Genetics Texas A&M Health Science Center Bryan Texas USA
  3. Department of Biomedical Engineering Texas A&M University College Station Texas USA
  4. Department Medical Physiology Texas A&M Health Science Center Bryan Texas USA
  5. Department of Materials Science and Engineering Texas A&M University College Station Texas USA
Institutions: Texas A&M Health Science Center (United States); Texas A&M University (United States)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), volume 13, issue 24, article e22926
Dates: received 12 November 2025; accepted 10 February 2026; published online 28 March 2026; in print April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.202522926 · PMID 41903119 · PMCID PMC13115983 · OpenAlex W7142140370
Open access: gold, a free copy (OpenAlex)
Categories: human (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: engineered extracellular matrix (eECM), glioblastoma multiforme (GBM), in vitro model, organoid, patient‐derived glioma stem‐like cells (GSC)
MeSH: Brain Neoplasms*, Extracellular Matrix*, Glioblastoma*, Organoids*, Humans, Neoplastic Stem Cells, Spheroids, Cellular, Tumor Microenvironment (* major topic)
Topic: Glioma Diagnosis and Treatment (Oncology, Medicine), according to OpenAlex
Citations: cited by 1 paper (Europe PMC); 102 references in the paper

Abstract

Glioblastoma multiforme (GBM) is an aggressive, angiogenic WHO grade IV glioma marked by rapid progression, therapeutic resistance, and poor prognosis. A defining feature of GBM is the presence of glioma stem‐like cells (GSC), which reside in specialized perivascular niches and drive tumor progression, recurrence, and therapeutic resistance. Current in vitro GBM models inadequately recapitulate the structural and biochemical cues of the native perivascular niche due to the absence of functional vasculature and brain‐mimetic extracellular matrix (ECM), limiting their physiological relevance and predictive power. To address the limitations of existing in vitro GBM models, we developed a patient‐derived GSC derived Matrigel spheroid system that transitions into organoids and enables integration into engineered microenvironments. Our model incorporates GSC spheroids representing proneural and mesenchymal GBM subtypes, a synthetic engineered extracellular matrix (eECM), and endothelial cells (EC) seeded on the matrix surface. Our results show that Matrigel‐derived GSC spheroids progressively differentiate over two weeks, with significantly enhanced expression of cell‐specific markers in the presence of EC. Encapsulation of these organoids within eECM, combined with EC co‐culture, further promoted induction of GBM‐associated genes. Together, this platform provides a modular in vitro system for investigating GBM pathophysiology.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available in Zenodo at https://doi.org/10.5281/zenodo.16907365, reference number 16907365.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 8 MeSH terms, 3 funders, 102 references, 15 RRIDs.

Cite

This paper

McManis, A., Jimenez, C. A., Shirolkar, A., Raza ur Rehman, S., Mallick, S., Murphy, M., Gaharwar, A. K., & Singh, I. (2026). Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(24), e22926. https://doi.org/10.1002/advs.202522926

BibTeX

@article{mcmanis2026understanding,
author = {McManis, Autumn and Jimenez, Charles Ashley and Shirolkar, Abha and Raza ur Rehman, Syed and Mallick, Sumana and Murphy, Malea and Gaharwar, Akhilesh K. and Singh, Irtisha},
title = {{Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = mar,
volume = {13},
number = {24},
pages = {e22926},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.202522926},
url = {https://doi.org/10.1002/advs.202522926},
pmid = {41903119},
pmcid = {PMC13115983}
}

RIS

TY - JOUR
AU - McManis, Autumn
AU - Jimenez, Charles Ashley
AU - Shirolkar, Abha
AU - Raza ur Rehman, Syed
AU - Mallick, Sumana
AU - Murphy, Malea
AU - Gaharwar, Akhilesh K.
AU - Singh, Irtisha
TI - Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/03/28
VL - 13
IS - 24
SP - e22926
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.202522926
UR - https://doi.org/10.1002/advs.202522926
LA - en
ER -

CSL-JSON

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