Background:Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models.Methods:We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice.Results:Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors.Conclusions:The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
背景:尽管采用多模式治疗,恶性脑肿瘤患者的预后仍然极差。开发有效疗法的主要障碍之一是缺乏临床相关且生物学精确(CRBA)的小鼠模型。方法:我们开发了一种徒手外科技术,能够快速安全地将新鲜人脑肿瘤样本直接注射到SCID小鼠大脑的对应部位(大脑、小脑或脑干)。结果:利用该技术,我们从408例脑肿瘤患者样本(包括高级别和低级别肿瘤)中成功建立了188个PDOX模型,其中高级别胶质瘤成功率为72.3%,髓母细胞瘤为64.2%,非典型畸胎样横纹肌样瘤为50%,室管膜瘤为33.8%,低级别胶质瘤为11.6%。详细表征证实这些模型成功复制了原始患者肿瘤的组织病理学和遗传学异常特征。结论:该方案无需立体定位框架,操作简便,可快速建立大批荷瘤小鼠模型,满足生物学研究和临床前药物测试的需求。