Qi Lin, Baxter Patricia, Kogiso Mari, Zhang Huiyuan, Braun Frank K, Lindsay Holly, Zhao Sibo, Xiao Sophie, Abdallah Aalaa Sanad, Suarez Milagros, Huang Zilu, Teo Wan Yee, Yu Litian, Zhao Xiumei, Liu Zhigang, Huang Yulun, Su Jack M, Man Tsz-Kwong, Lau Ching C, Perlaky Laszlo, Du Yuchen, Li Xiao-Nan
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University, Shenzhen 510080, China.
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Cancers (Basel). 2024 Apr 28;16(9):1716. doi: 10.3390/cancers16091716.
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. 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. 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. 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.
尽管采用了多模态疗法，但恶性脑肿瘤患者的预后仍然极差。阻碍有效疗法发展的主要障碍之一是缺乏临床相关且生物学准确的（CRBA）小鼠模型。我们开发了一种徒手手术技术，可将新鲜的人脑肿瘤标本快速安全地直接注射到SCID小鼠大脑的匹配位置（大脑、小脑或脑干）。使用该技术，我们成功地从408例脑肿瘤患者样本（包括高级别和低级别）中建立了188个患者来源的异种移植（PDOX）模型，高级别胶质瘤的成功率为72.3%，髓母细胞瘤为64.2%，非典型畸胎样/横纹肌样肿瘤（ATRT）为50%，室管膜瘤为33.8%，低级别胶质瘤为11.6%。详细的表征证实了它们复制了原始患者肿瘤的组织病理学和基因异常。该方案易于遵循，无需立体定向框架，以便生成大量荷瘤小鼠，满足生物学研究和临床前药物测试的需求。
