Affiliation:
1. Department of Precision and Microsystems Engineering Faculty of Mechanical Maritime and Materials Engineering Delft University of Technology Mekelweg 2 2628 CD Delft The Netherlands
2. Holland Proton Therapy Center (HollandPTC) Huismansingel 4 2629 JH Delft The Netherlands
3. Erasmus University College Nieuwemarkt 1A, Rotterdam 3011 HP Rotterdam The Netherlands
4. Einthoven Laboratory for Vascular and Regenerative Medicine Division of Thrombosis and Hemostasis Department of Internal Medicine Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands
Abstract
AbstractGlioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. While X‐ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can damage cancer cells while sparing the surrounding healthy tissue. However, the effects of protons on in vitro GBM models at the cellular level, especially when co‐cultured with endothelial cells, the building blocks of brain micro‐vessels, are still unexplored. In this work, novel 3D‐engineered scaffolds inspired by the geometry of brain microvasculature are designed, where GBM cells cluster and proliferate. The architectures are fabricated by two‐photon polymerization (2PP), pre‐cultured with endothelial cells (HUVECs), and then cultured with a human GBM cell line (U251). The micro‐vessel structures enable GBM in vivo‐like morphologies, and the results show a higher DNA double‐strand breakage in GBM monoculture samples when compared to the U251/HUVECs co‐culture, with cells in 2D featuring a larger number of DNA damage foci when compared to cells in 3D. The discrepancy in terms of proton radiation response indicates a difference in the radioresistance of the GBM cells mediated by the presence of HUVECs and the possible induction of stemness features that contribute to radioresistance and improved DNA repair.
Funder
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
2 articles.
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