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

Authors

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

Publication Date

4-28-2024

Journal

Cancers

DOI

10.3390/cancers16091716

PMID

38730671

PMCID

PMC11083000

PubMedCentral® Posted Date

4-28-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

orthotopic xenograft model, brain tumor, cancer

Abstract

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.