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- Title
Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development.
- Authors
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
- Abstract
Simple Summary: In this study, researchers tackled the challenge of advancing therapies for malignant brain tumors, given the scarcity of clinically relevant and biologically accurate mouse models. They introduced a novel surgical technique for transplanting fresh human brain tumor samples into SCID mice, accurately mimicking the original tumor's location in the brain. Through this method, they successfully established 188 patient-derived orthotopic xenograft (PDOX) models from 408 brain tumor samples, preserving the histopathological and genetic traits of the original tumors. Success rates varied among tumor types, with high-grade glioma demonstrating the highest success rate. Overall, this technique presents a straightforward and effective approach for generating extensive cohorts of tumor-bearing mice for both biological investigations and preclinical drug evaluations, eliminating the necessity for a stereotactic frame. 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.
- Subjects
BRAIN tumor genetics; RESEARCH funding; XENOGRAFTS; BIOLOGICAL products; DESCRIPTIVE statistics; CELL lines; MICE; ANIMAL experimentation; BRAIN tumors; HISTOLOGY
- Publication
Cancers, 2024, Vol 16, Issue 9, p1716
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16091716