Development and Characterization of Porcine Models of Glioma

Abstract

Development and Characterization of Porcine Models of glioma Muhibullah S. Tora 132 pages The development of porcine models of glioma using lentiviral vector mediated gene transfer was proposed. Lentiviral vectors were designed based on commonly implicated genetic pathways in high-grade glioma in the brain and spinal cord. Minipigs underwent either laminectomy or craniotomy with subsequent intraparenchymal administration of lentiviral vectors into respective white matter targets in the spinal cord or brain. Behavioral, motor, and clinical veterinary readouts were evaluated. Animals underwent magnetic resonance imaging and post-mortem tissue analyses including immunohistochemistry of tumor markers, RNA-sequencing, differential expression analysis, and gene set enrichment analysis. It was determined that the use of lentiviral mediated gene transfer in the minipig was a feasible approach to induce de-novo gliomagenesis in both the brain and spinal cord, with histopathologic and transcriptomic confirmation. Findings concerning each of the experimental metrics, implications on translation, limitations of the present models, and future research are discussed.