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Author Spotlight: Patient-Informed 3D Model for Studying Glioblastoma Invasion via Interstitial Fluid Flow
Published on: October 18, 2024
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Modeling cancer-associated hypercoagulability using glioblastoma spheroids in microfluidic chips
Maaike Y Kapteijn1, Monika Yanovska1, El Houari Laghmani1
1Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Research and Practice in Thrombosis and Haemostasis
|September 13, 2024
Summary
Glioblastoma significantly increases blood clot risk. A new cancer-on-a-chip model shows glioblastoma cells activate coagulation, offering a platform for developing new blood clot treatments.
Area of Science:
- Biomedical Engineering
- Oncology
- Hematology
Background:
- Glioblastoma poses a high risk (10-30%) for venous thromboembolism.
- Tumor-intrinsic factors influence vascular permeability and hypercoagulability.
- Novel models are needed to study cancer-associated thrombosis at the molecular level.
Purpose of the Study:
- To develop a novel cancer-on-a-chip model.
- To investigate the effects of glioblastoma cells on blood coagulation deregulation.
Main Methods:
- Co-culturing human umbilical vein endothelial cells with glioblastoma spheroids (U251 LV-TF or U251 LV-Ctrl).
- Utilizing an OrganoPlate Graft platform.
- Performing a modified thrombin generation assay within the cancer-on-a-chip model.
Main Results:
- Glioblastoma spheroids significantly increased the procoagulant state, elevating endogenous thrombin potential by 3.1-fold (U251 LV-Ctrl) and 7.0-fold (U251 LV-TF).
- The anticoagulant drug rivaroxaban and a tissue factor (TF) blocking antibody (5G9) effectively inhibited coagulation activation in the U251 LV-TF model, reducing endogenous thrombin potential by 4.0- and 4.4-fold, respectively.
Conclusions:
- A novel 3D cancer-on-a-chip model was developed.
- This model can aid in discovering new anticoagulant drugs.
- The model facilitates the identification of optimal anticoagulant strategies for glioblastoma and other cancers.
