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优化培养可获得高成功率并保留分子异质性，从而能够对高级别胶质瘤进行个性化筛查。

Optimized culturing yields high success rates and preserves molecular heterogeneity, enabling personalized screening for high-grade gliomas.

作者信息

Posthoorn-Verheul Cassandra, Fabro Federica, Ntafoulis Ioannis, den Hollander Chelsea, Verploegh Iris S C, Balvers Rutger, Kers Trisha V, Hoogeveen Jessica, van der Burg Judith, Eussen Bert, de Klein Annelies, Feller Kate J, Chien Miao-Ping, Dirven Clemens M F, Leenstra Sieger, Lamfers Martine L M

机构信息

Department of Neurosurgery, Brain Tumor Center, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.

Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands.

出版信息

NPJ Precis Oncol. 2025 May 27;9(1):156. doi: 10.1038/s41698-025-00946-1.

DOI:10.1038/s41698-025-00946-1
PMID:40425813
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12116786/
Abstract

To discover new treatment options for high-grade glioma (HGG), robust in vitro models are essential, but reliably establishing patient-derived cell cultures remains challenging. We established glioma stem-like cell (GSC) cultures from 114 consecutive HGG specimens via traditional surgical resection and/or ultrasonic aspiration, using completely dissociated single cell (single cell-derived, SCD) and partially dissociated 3D-derived (3DD) tissue fragments. Higher success rates in culture establishment were obtained from ultrasonic aspirates and 3DD surgical samples. Combining these approaches yielded a 96% success rate. Copy number profiling showed overall genetic similarities between cultures and parental tissue. Single-cell sequencing revealed greater transcriptomic heterogeneity in ultrasonic aspiration-derived cultures. Our protocol enabled the screening of 20 anti-cancer agents within a clinically relevant timeframe for 16 out of 18 HGG samples. This refined protocol serves as a robust tool for establishing HGG cell cultures that retain the molecular characteristics of the tumors and support applications in precision medicine.

摘要

为了发现高级别胶质瘤（HGG）的新治疗方案，强大的体外模型至关重要，但可靠地建立患者来源的细胞培养物仍然具有挑战性。我们通过传统手术切除和/或超声抽吸，使用完全解离的单细胞（单细胞衍生，SCD）和部分解离的3D衍生（3DD）组织片段，从114例连续的HGG标本中建立了胶质瘤干细胞样细胞（GSC）培养物。从超声抽吸物和3DD手术样本中获得了更高的培养成功率。结合这些方法成功率达到了96%。拷贝数分析显示培养物与亲本组织之间总体遗传相似性。单细胞测序揭示了超声抽吸来源的培养物中更大的转录组异质性。我们的方案能够在临床相关时间范围内对18个HGG样本中的16个进行20种抗癌药物的筛选。这种优化的方案是建立保留肿瘤分子特征并支持精准医学应用的HGG细胞培养物的强大工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/9f2963db8048/41698_2025_946_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/401987501258/41698_2025_946_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/ed3166b1cfff/41698_2025_946_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/8fa5a9f79fb4/41698_2025_946_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/d4f1b5524bf1/41698_2025_946_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/9e37c75cbf51/41698_2025_946_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/9f2963db8048/41698_2025_946_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/401987501258/41698_2025_946_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/ed3166b1cfff/41698_2025_946_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/8fa5a9f79fb4/41698_2025_946_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/d4f1b5524bf1/41698_2025_946_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/9e37c75cbf51/41698_2025_946_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c07/12116786/9f2963db8048/41698_2025_946_Fig6_HTML.jpg

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Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers.体外药物敏感性筛选可预测胶质母细胞瘤患者对替莫唑胺的反应，并鉴定候选生物标志物。
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The Future Glioblastoma Clinical Trials Landscape: Early Phase 0, Window of Opportunity, and Adaptive Phase I-III Studies.
未来胶质母细胞瘤临床试验格局：早期 0 期、机会之窗和适应性 I-III 期研究。
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