Lentiviral Vector-Induced Modeling of Low-Grade Glioma in the Minipig Spinal Cord

Spinal cord gliomas span a broad biological spectrum, from aggressive high-grade to indolent low-grade tumors, yet clinically relevant large animal models of low-grade disease remain scarce. Building on our established minipig high-grade spinal cord glioma model (lentiviral delivery of PDGFB, HRAS, and TP53), we sought to develop a complementary low-grade model on the same platform.

Two cohorts of minipigs (N=4 per group) received intraspinal lentiviral injections targeting PDGFB with TP53 knockdown (Group 1) or PDGFB, BRAF V600E, and TP53 knockdown (Group 2). Per a pre-specified protocol, MRI was performed only in animals with persistent altered ambulation; all animals underwent terminal histopathology at a fixed 180-day endpoint.

Both groups developed spinal cord lesions with a histologically low-grade phenotype, in contrast to our previously characterized high-grade model. Histopathologic tumor penetrance was 100% (8/8). Group 1 lesions were diffusely infiltrative, with uniform tumor cells, tissue edema, and no necrosis or vascular proliferation, consistent with a low-grade astrocytic phenotype. Group 2 lesions showed heterogeneous, biphasic morphology combining diffuse gliomatous and spindle-cell components with increased nuclear atypia. Behavioral deficits were mild and largely transient; 2 of 8 animals met MRI criteria (both Group 2), and a mass-forming, contrast-enhancing intramedullary lesion was identified in 1.

These data provide proof-of-concept for a minipig model of low-grade spinal cord glioma, offering a clinically scaled large animal platform for studying low-grade glioma biology. Larger cohorts, prospective interval imaging, and molecular validation against human spinal cord glioma datasets are needed to establish translational fidelity.