Introduction:Meningiomas are the most common primary central nervous system tumors, constituting 39.7% of intracranial tumors. Although generally benign, some exhibit aggressive behavior and risk of recurrence, necessitating adjuvant therapy and repeat surgical interventions. Molecular studies have identified tumor-driving mutations, leading to targeted therapies and clinical trials. However, translating preclinical findings into clinical success is often hindered by limitations in current meningioma tumor models. This study aims to develop and validate a standardized protocol for establishing patient-derived meningioma organoids (MEN-Os) that faithfully replicate human disease.Methods:MEN-Os were successfully established from 15 meningioma samples (11 grade 1, 4 grade 2) from neurosurgical resections using an optimized culture protocol. Histological and immunohistochemical analyses were used to assess the resemblance of MEN-Os to original tumor tissues. RNA sequencing compared transcriptional signatures between MEN-Os and corresponding patient-resected tissues.Results:MEN-Os were successfully established from patient-resected samples and maintained in culture for up to four weeks, showing stable growth and structural integrity. Histopathological analysis revealed that MEN-Os preserved key architectural features, including cellular organization, nuclear morphology, and proliferation rates. Immunohistochemical staining for meningioma-specific markers, such as the progesterone receptor, confirmed similar expression patterns to parental tumors. Transcriptomic profiling demonstrated that MEN-Os retained the transcriptional signatures of original tissues, including genes associated with meningioma pathology (NF2, CDKN2A, TP53). Differential expression and deconvolution analyses showed that MEN-Os contained diverse cell populations, including tumor and stromal cells, while preserving the immune microenvironment, as validated by histopathological and transcriptomic profiling.Conclusion:We established a robust, reproducible protocol for generating MEN-Os, which faithfully replicates the histopathological, molecular, and cellular characteristics of original tumors. MEN-Os provide a valuable model for studying meningioma biology and evaluating therapeutic strategies.
引言：脑膜瘤是最常见的原发性中枢神经系统肿瘤，占颅内肿瘤的39.7%。尽管通常为良性，但部分脑膜瘤表现出侵袭性行为及复发风险，需要辅助治疗和重复手术干预。分子研究已鉴定出驱动肿瘤发生的突变，推动了靶向治疗和临床试验的发展。然而，当前脑膜瘤肿瘤模型的局限性常常阻碍临床前研究成果向临床成功转化。本研究旨在开发并验证一套标准化方案，用于建立能够忠实模拟人类疾病的患者源性脑膜瘤类器官模型。 方法：通过优化的培养方案，成功利用神经外科切除的15例脑膜瘤样本（11例1级，4例2级）建立了脑膜瘤类器官。采用组织学和免疫组化分析评估类器官与原发肿瘤组织的相似性，并通过RNA测序比较类器官与对应患者切除组织的转录特征。 结果：从患者切除样本中成功建立脑膜瘤类器官，并在培养中维持长达四周，表现出稳定的生长和结构完整性。组织病理学分析显示类器官保留了关键结构特征，包括细胞组织结构、核形态和增殖率。针对脑膜瘤特异性标志物（如孕激素受体）的免疫组化染色证实其表达模式与亲本肿瘤相似。转录组分析表明类器官保留了原始组织的转录特征，包括与脑膜瘤病理相关的基因（NF2、CDKN2A、TP53）。差异表达分析和反卷积分析显示，类器官包含肿瘤细胞与基质细胞在内的多种细胞群，同时保留了免疫微环境特征，这些发现均通过组织病理学和转录组分析得到验证。 结论：我们建立了一套稳定、可重复的脑膜瘤类器官生成方案，该模型能忠实再现原始肿瘤的组织病理学、分子及细胞特征。脑膜瘤类器官为研究脑膜瘤生物学特性及评估治疗策略提供了重要模型。
Patient-Derived Meningioma Organoids: A Reliable Model for Studying Human Tumor Pathophysiology
肿瘤(癌症)患者之家