Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development

将患者脑肿瘤细胞直接植入小鼠脑内匹配位置,以建立患者原位异种移植模型

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作者:Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M Su, Tsz-Kwong Man, Ching C Lau, Laszlo Perlaky, Yuchen Du, Xiao-Nan Li

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.

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.

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.

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