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Updated: Dec 14, 2025
Creating Anatomically Accurate and Reproducible Intracranial Xenografts of Human Brain Tumors
Published on: September 24, 2014
Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies
Amber E Kerstetter-Fogle1,2, Peggy L R Harris1,2, Susann M Brady-Kalnay2,3
1Department of Neurological Surgery, Case Western Reserve University and University Hospitals Cleveland, OH 44106, USA.
Abstract:
Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, the high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have established orthotopic patient-derived xenografts (PDX) from 37 GBM patients with human GBM. Of the 69 patient samples analyzed, we were successful in passaging 37 lines three or more generations (53.6%). After phenotypic characterization of the xenografted tumor tissue, two different growth patterns emerged highly invasive or localized. The phenotype was dependent on malignancy and previous treatment of the patient from which the xenograft was derived. Physiologically, mice exhibited symptoms more quickly with each subsequent passage, particularly in the localized tumors. Study of these physiologically relevant human xenografts in mice will enable therapeutic screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which may eventually be used for simulating treatment.
Insights
Patient-derived xenografts (PDX) from glioblastoma multiforme (GBM) offer a more accurate model of brain cancer. These models better mimic the human tumor microenvironment for improved therapeutic development.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain cancer with limited therapeutic options.
- Current cell culture models fail to replicate the complex brain microenvironment and molecular signatures of GBM.
- This leads to a high failure rate of therapies transitioning from lab to clinic.
Purpose of the Study:
- To establish and characterize orthotopic patient-derived xenografts (PDX) from human GBM.
- To create physiologically relevant models that recapitulate GBM's in vivo tumor microenvironment.
- To enable more accurate preclinical therapeutic screening for glioblastoma.
Main Methods:
- Xenotransplantation of 69 human GBM patient samples into immunocompromised mice.
- Establishment of orthotopic patient-derived xenografts (PDX) from successful samples.
- Phenotypic characterization of xenografted tumor tissue, including growth patterns (invasive vs. localized).
Main Results:
- Successfully established 37 GBM PDX lines from 69 patient samples (53.6% success rate).
- Identified two distinct tumor growth patterns: highly invasive and localized.
- Observed accelerated disease progression in mice with subsequent tumor passages, particularly for localized tumors.
Conclusions:
- GBM patient-derived xenografts (PDX) provide a more accurate preclinical model than traditional cell cultures.
- These models reflect tumor heterogeneity and the in vivo microenvironment, crucial for understanding GBM.
- PDX models hold promise for advancing glioblastoma treatment strategies and personalized medicine.
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