An ex-vivo multiple sclerosis model of inflammatory demyelination using hyperbranched polymer

Asha Mathew, Janelle M. P. Pakan, Estelle C. Collin, Wenxin Wang, Kieran W. McDermott, Una Fitzgerald, Richard Reynolds, Abhay S. Pandit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple sclerosis (MS) is characterized by the presence of inflammatory demyelinating foci throughout the brain and spinal cord, accompanied by axonal and neuronal damage. Although inflammatory processes are thought to underlie the pathological changes, the individual mediators of this damage are unclear. In order to study the role of pro-inflammatory cytokines in demyelination in the central nervous system, we have utilized a hyperbranched poly(2-dimethyl-aminoethylmethacrylate) based non-viral gene transfection system to establish an inflammatory demyelinating model of MS in an ex-vivo environment. The synthesized non-viral gene transfection system was optimized for efficient transfection with minimal cytotoxicity. Organotypic brain slices were then successfully transfected with the TNF or IFN gamma genes. TNF and IFN gamma expression and release in cerebellar slices via non-viral gene delivery approach resulted in inflammation mediated myelin loss, thus making it a promising ex-vivo approach for studying the underlying mechanisms of demyelination in myelin-related diseases such as MS. (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)5872-5882
Number of pages11
JournalBiomaterials
Volume34
Issue number23
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Non-viral gene delivery
  • Organotypic brain slice
  • Multiple sclerosis
  • Demyelination
  • Inflammation
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • ANTIBODY-MEDIATED DEMYELINATION
  • MESSENGER-RNA EXPRESSION
  • CENTRAL-NERVOUS-SYSTEM
  • NECROSIS-FACTOR-ALPHA
  • INTERFERON-GAMMA
  • GENE-TRANSFER
  • MENINGEAL INFLAMMATION
  • CEREBROSPINAL-FLUID
  • EXPLANT CULTURES

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