Zheng Chengjun, Wang Peng, Zhang Delong, Fang Zheng, Feng Yutong, Chen Jie, Chen Jiahong, Fu Yiwen, Yang Bao, Yu Shuqing, Min Li, Xiao Bo, Xing Cencan, Yang Yang, Wang Jianfeng, Zou Donghua, Ning Shipeng, Liu Tong, Yan Jun, Zhao Qian, Sun Fei, Chen Qiaodong, Zhang Ying, Jiang Tao, Zheng Lemin, Bao Zhaoshi
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Bioact Mater. 2025 Jul 14;53:205-217. doi: 10.1016/j.bioactmat.2025.07.015. eCollection 2025 Nov.
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.
胶质瘤是一种侵袭性脑肿瘤，预后较差。建立一种能紧密复制原始肿瘤细胞组成和微环境的体外培养模型一直具有挑战性，限制了其临床应用。在此，我们提出一种从患者来源的胶质瘤组织生成具有微环境的胶质瘤类器官（GlioME）的新方法。这些类器官保留了原发肿瘤的遗传和表观遗传特征，并维持肿瘤微环境内的细胞间相互作用，包括驻留免疫细胞。采用批量RNA测序、全外显子组测序和DNA甲基化分析来确认类器官与原发性胶质瘤组织之间的分子相似性。利用免疫荧光和流式细胞术评估免疫细胞活力，将GlioME与悬浮胶质瘤类器官进行比较。GlioME对化疗和靶向治疗表现出高反应性，证明了其在治疗筛选应用中的潜力。值得注意的是，GlioME准确预测了患者对最近获批的MET抑制剂维布替尼的反应。因此，这种类器官模型为胶质瘤微环境相关研究和临床药物筛选提供了一个可靠的体外平台。
