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

Author:

Qi Lin1234ORCID,Baxter Patricia23,Kogiso Mari23,Zhang Huiyuan23,Braun Frank K.23ORCID,Lindsay Holly23,Zhao Sibo23ORCID,Xiao Sophie4,Abdallah Aalaa Sanad4ORCID,Suarez Milagros4,Huang Zilu4,Teo Wan Yee25ORCID,Yu Litian23,Zhao Xiumei23,Liu Zhigang23ORCID,Huang Yulun23,Su Jack M.2,Man Tsz-Kwong2,Lau Ching C.2,Perlaky Laszlo2,Du Yuchen2346,Li Xiao-Nan2345

Affiliation:

1. Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University, Shenzhen 510080, China

2. Texas Children’s Cancer Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USA

3. Laboratory of Molecular Neuro-Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USA

4. Ann & Robert H. Lurie Children’s Hospital of Chicago, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

5. The Laboratory of Pediatric Brain Tumor Research Office, SingHealth Duke-NUS Academic Medical Center, Singapore 169856, Singapore

6. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA

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.

Funder

NIH/NCI Pediatric Preclinical Testing Consortium UO1

NIH/NCI Patient-Derived Models of Cancer

NIH/NCI Pediatric Preclinical In Vivo Testing Program

Cancer Prevention & Research Institute of Texas

CDMRP DOD PRCRP

St. Baldrick’s Foundation

Publisher

MDPI AG

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