侵攻性脳腫瘍に対する陽子線治療の効果を研究する新しい3D共培養モデル(New 3D co-culture model to study the effect of proton therapy on aggressive brain cancer)

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2023-12-08 オランダ・デルフト工科大学(TUDelft)

◆アンジェロ・アッカルド氏は、がん研究において2D環境や動物実験の制約を超え、3Dエンジニアリングスキャフォールドを開発しました。これは、プロトン線放射線のギャップを埋め、グリオブラストーマに与える影響を理解するための微細な脳の微小血管構造を模したものです。
◆この3Dモデルは、プロトンががん細胞に与える影響をin vivoモデルに近い結果で再現し、プロトン線放射線生物学の新しい基準ツールとなり得ます。アッカルド氏の最終目標は、このモデルを使用してがん細胞の放射線応答を調査し、個別化された治療戦略を実現することです。

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膠芽腫の陽子線生物学を研究するための微小血管に似た3D足場-内皮細胞共培養モデル Micro-Vessels-Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma-Endothelial Cells Co-Culture Models

Qais Akolawala, Floor Keuning, Marta Rovituso, Wouter van Burik, Ernst van der Wal, Henri H. Versteeg, Araci M. R. Rondon, Angelo Accardo
Advanced Healthcare Materials  Published: 09 November 2023
DOI:https://doi.org/10.1002/adhm.202302988

Details are in the caption following the image

Abstract

Glioblastoma (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.

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