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A novel organoid model retaining the glioma microenvironment for personalized drug screening and therapeutic evaluation

作者:Chengjun Zheng, Pengli Wang, Delong Zhang, Zheng Fang, Yutong Feng, Jie Chen, Jiahong Chen, Yiwen Fu, Bao Yang, Shuqing Yu, Min Li, Bo Xiao, Cencan Xing, Yang Yang, Jianfeng Wang, Donghua Zou, Shipeng Ning, Tong Liu, Jun Yan, Qian Zhao, Fei Sun, Qiaodong Chen, Ying Zhang, Tao Jiang, Lemin Zheng, Zhaoshi Bao · 发表于:Bioactive Materials · 年份:2025 · DOI:10.1016/j.bioactmat.2025.07.015 · 被引用次数:8 · 研究领域:Glioma Diagnosis and Treatment、Mathematical Biology Tumor Growth、Immune cells in cancer

Glioma is an aggressive brain tumor with a poor prognosis. Establishing an in vitro culture model that closely replicates the cellular composition and microenvironment of the original tumor has been challenging, limiting its clinical applications. Here, we present a novel approach to generate glioma organoids with a microenvironment (GlioME) from patient-derived glioma tissue. These organoids maintain the genetic and epigenetic characteristics of the primary tumor and preserve cell-to-cell interactions within the tumor microenvironment, including resident immune cells. Bulk RNA sequencing, whole exome sequencing, and DNA methylation analysis were used to confirm the molecular similarities between the organoids and primary glioma tissues. Immunofluorescence and flow cytometry were used to assess immune cell viability, comparing GlioME with floating glioma organoids. GlioME exhibited high responsiveness to chemotherapy and targeted therapy, demonstrating its potential for therapeutic screening applications. Notably, GlioME accurately predicted patient response to the recently approved MET inhibitor, vebreltinib. Thus, this organoid model provides a reliable in vitro platform for glioma microenvironment-related research and clinical drug screening.