Terasaki Institute researchers develop a 3D microphysiological system modeling pericyte-induced chemoresistance in glioblastoma

Los Angeles, CA - May 27, 2025  – Scientists at the Terasaki Institute for Biomedical Innovation (TIBI), led by Dr. Vadim Jucaud (Assistant Professor), have engineered a novel multi-cellular 3D glioblastoma (GBM) in vitro model that mimics the biomechanical properties of brain tissue and the role of pericytes in glioblastoma (GBM) resistance to temozolomide (TMZ), the standard-of-care chemotherapy for this deadly brain cancer.

This novel in vitro model, published this week in Acta Biomaterialia, integrates human GBM tumor cells and pericytes, a type of supportive cell in the brain, within a biomaterial that closely mimics the brain's physicochemical and diffusive properties. The model was applied to three distinct GBM cell lines co-cultured with primary pericytes to confirm the influence of pericytes on GBM chemoresistance. When GBM cells were cultured with pericytes in the engineered biomaterial, their resistance to TMZ increased significantly across different cell lines, by 22% to over 32%. This enhanced chemoresistance was linked to a 160-fold increase in pericyte expression of CCL5, a chemokine associated with inflammatory signaling, cell survival, and ultimately, TMZ resistance.

"By recreating not just the cellular makeup but also the tissue-level mechanical properties of the brain, this 3D GBM model provides a more accurate framework to study drug response and resistance," said Dr. Vadim Jucaud. "Our model could be used for the screening of standard-of-care chemotherapies, or the discovery of novel drugs, particularly those targeting the CCL5 signaling axis."

Other salient findings include the differential sensitivity of GBM cell lines to TMZ and its off-target toxicity, confirming that this platform allows for the evaluation of drug response under conditions that better reflect the in vivo GBM tumor microenvironment.

"This model represents a powerful preclinical tool that captures key elements of tumor biology often overlooked in simpler systems," said Dr. Ali Khademhosseini, CEO of TIBI. "It opens the door to more accurate drug screening and better understanding of resistance mechanisms in GBM."

Beyond advancing fundamental knowledge of GBM biology, this biomimetic platform offers a scalable, cost-effective alternative to animal testing, enabling high-throughput drug screening and individualized treatment testing.

To read the published article, visit https://www.sciencedirect.com/science/article/abs/pii/S1742706125003630?via%3Dihub

For more information about the Terasaki Institute's work in cancer biology and regenerative medicine, visit www.terasaki.org.

For more information about this research, please contact:

Dr. Vadim Jucaud

Terasaki Institute for Biomedical Innovation

Email: vjucaud@terasaki.org

About the Terasaki Institute for Biomedical Innovation:

The Terasaki Institute for Biomedical Innovation (terasaki.org) is a non-profit research organization that invents and fosters practical solutions that restore or enhance the health of individuals. The Institute is made possible through an endowment from the late Dr. Paul I. Terasaki, a pioneer in organ transplant technology.

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