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Author Notes:

Corresponding author:Muhibullah S. Tora, Email:mtora@emory.edu

Study conception and design were performed by M.S.T., P.T., T.F., J.N.B., P.C., J.N.O. and N.M.B.

Surgeries, animal care, tissue extractions, vector preparations, and overall experiments were performed by M.S.T., P.T., J.W., R.J., R.S.R., N.H., P.P.N., A.K., C.R., T.F., J.N.O. and N.M.B.

Data analysis and interpretation were performed by M.T., P.T., T.F., S.N., P.C., P.P.N., J.N.B., J.N.O. and N.M.B. Manuscript drafting and figure preparation were performed by M.S.T. and P.T.

All authors reviewed the manuscript.

The authors acknowledge the numerous faculty and staff of the Division of Animal Resources (DAR) and the Emory Center for Systems Imaging (CSI) for their guidance, expertise, and assistance on the present study.

In addition, we acknowledge the support of the Emory Integrated Genomics Core (EIGC).

The authors declare no competing interests.

Subject:

Research Funding:

we acknowledge the support of the Emory Neuroscience Neuropathology Core, which is supported by the NINDS Core Facilities Grant P30NS055077.

Funding for this study was provided by a generous grant from the Gluck Foundation.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • CONVECTION-ENHANCED DELIVERY
  • GROWTH-FACTOR
  • AUTOCRINE STIMULATION
  • GENE-TRANSFER
  • GLIOBLASTOMA
  • PIG
  • DRIVEN
  • HETEROGENEITY
  • PROGENITORS
  • XENOGRAFT

Lentiviral Vector Induced Modeling of High-Grade Spinal Cord Glioma in Minipigs

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Journal Title:

Scientific Reports

Volume:

Volume 10, Number 1

Publisher:

, Pages 5291-5291

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Prior studies have applied driver mutations targeting the RTK/RAS/PI3K and p53 pathways to induce the formation of high-grade gliomas in rodent models. In the present study, we report the production of a high-grade spinal cord glioma model in pigs using lentiviral gene transfer. Methods: Six Gottingen Minipigs received thoracolumbar (T14-L1) lateral white matter injections of a combination of lentiviral vectors, expressing platelet-derived growth factor beta (PDGF-B), constitutive HRAS, and shRNA-p53 respectively. All animals received injection of control vectors into the contralateral cord. Animals underwent baseline and endpoint magnetic resonance imaging (MRI) and were evaluated daily for clinical deficits. Hematoxylin and eosin (H&E) and immunohistochemical analysis was conducted. Data are presented using descriptive statistics including relative frequencies, mean, standard deviation, and range. Results: 100% of animals (n = 6/6) developed clinical motor deficits ipsilateral to the oncogenic lentiviral injections by a three-week endpoint. MRI scans at endpoint demonstrated contrast enhancing mass lesions at the site of oncogenic lentiviral injection and not at the site of control injections. Immunohistochemistry demonstrated positive staining for GFAP, Olig2, and a high Ki-67 proliferative index. Histopathologic features demonstrate consistent and reproducible growth of a high-grade glioma in all animals. Conclusions: Lentiviral gene transfer represents a feasible pathway to glioma modeling in higher order species. The present model is the first lentiviral vector induced pig model of high-grade spinal cord glioma and may potentially be used in preclinical therapeutic development programs.

Copyright information:

© 2020, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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