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| 基于人源胶质母细胞瘤的肿瘤类器官的构建及鉴定 |
| 吕宗强1,2,王洪祥1,孙波1,罗宁1,李荣1,王春琳2*,陈菊祥1* |
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(1. 海军军医大学(第二军医大学)第一附属医院神经外科, 上海 200433;
2. 中国人民解放军联勤保障部队第九〇一医院神经外科, 合肥 230031
*通信作者) |
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| 摘要: |
| 目的 建立和鉴定成熟稳定的胶质母细胞瘤（GBM）类器官，为GBM的研究和诊治提供准确和个体化的临床前模型。方法 通过外科手术获得患者来源新鲜GBM组织样本，经初步处理后，利用干细胞培养基分选出胶质母细胞瘤干细胞（GSC）并对其进行鉴定。将GSC在类器官培养基中进行三维培养、传代，成功培养出GBM类器官。通过H-E染色观察GBM类器官组织学形态，通过免疫荧光染色进行干性和亲本肿瘤相似性鉴定，通过裸小鼠原位成瘤实验对其进行体内原位成瘤能力鉴定。结果 从9例人源GBM样本中构建了7个GBM类器官，其形态似“神经球”，平均类器官形成时间为1周。H-E染色结果显示，GBM类器官在高倍镜下的组织学形态与GBM肿瘤组织极为相似；免疫荧光染色结果表明，GBM类器官具有干性特征及组织细胞学相似性；裸小鼠原位成瘤实验结果显示，GBM类器官相比于普通GBM细胞成瘤能力更强。结论 本研究成功构建了人源GBM类器官，该类器官保留了原始GBM组织细胞学特征，为未来GBM的研究与诊疗提供了新的模型。 |
| 关键词: 胶质母细胞瘤 胶质母细胞瘤干细胞 类器官 胶质母细胞瘤类器官 |
| DOI：10.16781/j.CN31-2187/R.20240770 |
| 投稿时间：2024-11-13修订日期：2025-02-18 |
| 基金项目:国家自然科学基金（82272715，82272904），上海市科学技术委员会科研计划项目（19JC1415000）. |
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| Construction and identification of tumor organoids derived from human glioblastoma |
| Lü Zongqiang1,2,WANG Hongxiang1,SUN Bo1,LUO Ning1,LI Rong1,WANG Chunlin2*,CHEN Juxiang1* |
(1. Department of Neurosurgery, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. Department of Neurosurgery, No. 901 Hospital of Joint Logistics Support Force of PLA, Hefei 230031, Anhui, China
*Corresponding authors) |
| Abstract: |
| Objective To establish and verify a mature and stable glioblastoma (GBM) organoid model, so as to provide an accurate and personalized preclinical model for the research and treatment of GBM. Methods Fresh GBM tissues obtained through surgical procedures were initially processed, and then GBM stem cells (GSCs) were isolated using stem cell culture medium and were identified. Subsequently, GSCs were cultured in organoid culture medium for 3D cultivation, and GBM organoids were successfully obtained. The histological morphology of GBM organoids was observed by hematoxylin-eosin (H-E) staining; the stemness and similarity to the parental tumor were identified by immunofluorescence staining; and the in vivo tumorigenic ability of GBM organoids was identified by orthotopic tumorigenesis experiments in nude mice. Results A total of 7 GBM organoids were constructed from 9 human GBM samples, with a morphology resembling “neurosphere”, and the average duration for organoid formation was 1 week. H-E staining results showed that the histological morphology of GBM organoids under high-power microscope was very similar to that of GBM tumor tissues; immunofluorescence staining results indicated that the GBM organoids possessed stemness characteristics and histological cellular similarity; and GBM organoids had a stronger tumorigenic ability compared to ordinary GBM cells in nude mice. Conclusion This study presents a stable and reliable method for constructing GBM organoids retaining the histological characteristics of the original GBM tissue, which providing new insights for future GBM research and clinical practice. |
| Key words: glioblastoma glioblastoma stem cells organoids glioblastoma organoids |
