Stereotactic Intracranial Implantation of Glioblastoma Patient-derived Xenograft Cell Lines in Mice
Danielle M Burgenske1, Lauren L Ott2, Katrina K Bakken2
1Mayo Clinic, Rochester; burgenske.danielle@mayo.edu.
Abstract:
The development of efficacious treatment regimens has been challenging for central nervous system tumors, in part due to the limited availability of translationally relevant preclinical models. Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is the focus of this research. Established cell line-derived models do not accurately reflect the genetic heterogeneity of human diseases. This is of particular concern in the current landscape, where a majority of pharmaceuticals are targeting tumor-specific alterations. Moreover, studies that leverage subcutaneous xenografts are technically easier to execute, but the blood-brain barrier (BBB) is completely absent. As one of the features responsible for treatment failure in neuro-oncology, the BBB must be considered when evaluating any novel therapeutic strategy. Therefore, intracranial placement is of critical importance. We have established and characterized over 100 GBM patient-derived xenograft (PDX) intracranial models to support therapeutic evaluation efforts. Here, we describe the stereotactic implantation technique that we utilize for these studies.
Insights
Developing effective glioblastoma (GBM) treatments requires better preclinical models. This study details a stereotactic implantation technique for over 100 patient-derived xenograft intracranial models, crucial for evaluating new neuro-oncology therapies.
Area of Science:
- Neuro-oncology
- Preclinical Cancer Models
- Translational Research
Background:
- Central nervous system (CNS) tumor treatment is hindered by a lack of translationally relevant preclinical models.
- Glioblastoma (GBM), a highly aggressive brain tumor, exhibits genetic heterogeneity not captured by traditional cell line models.
- Subcutaneous xenografts lack the blood-brain barrier (BBB), a critical factor in neuro-oncology treatment failure.
Purpose of the Study:
- To address the limitations of existing preclinical models for CNS tumors.
- To establish and characterize a robust collection of Glioblastoma patient-derived xenograft (PDX) intracranial models.
- To describe the stereotactic implantation technique used for creating these critical models.
Main Methods:
- Establishment and characterization of over 100 Glioblastoma patient-derived xenograft (PDX) models.
- Intracranial implantation of PDX models using stereotactic techniques.
- Evaluation of PDX models for translational relevance in therapeutic studies.
Main Results:
- Successfully established and characterized over 100 GBM PDX intracranial models.
- Developed a reliable stereotactic implantation technique for intracranial xenografts.
- These models accurately reflect human GBM genetic heterogeneity and the tumor microenvironment, including the BBB.
Conclusions:
- Patient-derived xenograft (PDX) intracranial models are essential for advancing neuro-oncology drug development.
- The described stereotactic implantation technique facilitates the creation of reliable GBM preclinical models.
- These models provide a platform for evaluating novel therapeutic strategies that account for the BBB.
