Lentiviral vector induced modeling of low grade glioma in the minipig spinal cord

Gliomas represent a diverse spectrum of central nervous system tumors, ranging from aggressive high-grade gliomas (HGG) to less aggressive low-grade gliomas (LGG). Our group previously developed a high-grade glioma model in the minipig spinal cord using PDGFB, HRAS, and TP53. We now report the development of a minipig low-grade glioma model. Lentiviral vectors gene expression of PDGFB, BRAF V600E, and TP53 were used to generate the low-grade glioma model. Disease progression was monitored through behavioral assessment, MRI imaging for lesion detection, and histopathological analysis. Unlike the previously characterized high-grade phenotype, these models demonstrated a distinct, less aggressive low-grade phenotype. Both groups developed spinal cord lesions with divergent histological features: Group 1 (PDGFB + shTP53) displayed diffusely infiltrative gliomas with uniform tumor cells, edema, and minimal necrosis, while Group 2 (PDGFB + BRAF V600E + shTP53) exhibited heterogeneous lesions combining diffuse gliomatous and spindle cell components with increased atypia, apoptosis, and greater axial involvement. These spindle cells appear to originate from myeloid rather than glial lineage. This work establishes the first minipig low-grade glioma model, providing a clinically relevant large animal system for investigating low-grade glioma biology and developing novel therapeutic interventions for spinal cord tumors.