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Lentiviral-Induced Spinal Cord Gliomas in Rat Model
Purva P Nagarajan1, Muhibullah S Tora1,2, Stewart G Neill3
1Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
International Journal of Molecular Sciences
|December 10, 2021
Summary
A novel rat model for high-grade spinal cord glioma was developed using a triple cocktail of PDGF-B, HRAS, and p53 knockdown vectors. This model efficiently replicates aggressive tumor characteristics, offering a promising platform for future therapeutic evaluations.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Animal Models
Background:
- Intramedullary spinal cord tumors are rare, understudied, and have limited treatment options.
- Previous research utilized a combination of PDGF-B, HRAS, and p53 knockdown in minipigs to induce high-grade glioma.
- This study aimed to create and characterize a more efficient rodent model for spinal cord glioma.
Purpose of the Study:
- To evaluate the efficacy of individual and combined lentiviral vectors (PDGF-B, HRAS, sh-p53) in generating high-grade spinal cord gliomas in rats.
- To compare the resulting tumor models based on behavioral, physiological, and histological outcomes.
- To establish a preclinical rat model for testing novel therapeutic strategies against spinal cord gliomas.
Main Methods:
- Rats underwent thoracolumbar laminectomy and injection of lentiviral vectors expressing PDGF-B, HRAS, sh-p53, or control vectors.
- Animals were monitored for 98 days for clinical deficits using scoring systems (Basso Beattie Bresnahan, Tarlov), weight, and survival.
- Tumor development was assessed via histological analysis (H&E) and immunohistochemistry (IHC) for proliferation (Ki67) and glial markers (GFAP, SOX2).
Main Results:
- The triple cocktail (PDGF-B+HRAS+sh-p53) induced significant declines in behavioral measures and survival rates compared to controls.
- Histological analysis confirmed tumor development in most groups, with the triple cocktail showing the most aggressive growth and pathological features.
- Immunohistochemistry revealed the highest increase in Ki67 proliferation and GFAP positivity in the triple cocktail group; PDGF-B+HRAS also showed increased proliferation, while PDGF-B and PDGF-B+sh-p53 showed increased SOX2 staining.
Conclusions:
- Different lentiviral vector combinations yield distinct high-grade spinal cord glioma models in rats.
- The triple cocktail (PDGF-B+HRAS+sh-p53) provides a highly efficient and aggressive preclinical model for spinal cord glioma.
- This rat model holds potential for evaluating future therapeutic interventions for this rare cancer.
