Local Immunomodulation with Anti-inflammatory Cytokine-Encoding Lentivirus Enhances Functional Recovery after Spinal Cord Injury

Jonghyuck Park, Joseph T. Decker, Daniel J. Margul, Dominique R. Smith, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Trauma to the spinal cord and associated secondary inflammation can lead to permanent loss of sensory and motor function below the injury level, with the resulting environment serving as a barrier that limits regeneration. In this study, we investigate the localized expression of anti-inflammatory cytokines IL-10 and IL-4 via lentiviral transduction in multichannel bridges. Porous multichannel bridges provide physical guidance for axonal outgrowth with the cytokines hypothesized to modulate the neuroinflammatory microenvironment and enhance axonal regeneration. Gene expression analyses indicated that induced IL-10 and IL-4 expression decreased expression of pro-inflammatory genes and increased pro-regenerative genes relative to control. Moreover, these factors led to increased numbers of axons and myelination, with approximately 45% of axons myelinated and the number of oligodendrocyte myelinated axons significantly increased by 3- to 4-fold. Furthermore, the combination of a bridge with IL-10 and IL-4 expression improved locomotor function after injury to an average score of 6 relative to an average score of 3 for injury alone. Collectively, these studies highlight the potential for localized immunomodulation to decrease secondary inflammation and enhance regeneration that may have numerous applications. Following spinal cord injury (SCI), secondary inflammatory responses further impair locomotor and sensory functions. In this study, the authors investigate nerve regeneration after SCI via local immunomodulation using lentiviral vector delivery of anti-inflammatory cytokines from a multichannel bridge as to initiate a regenerative program that overcomes multiple barriers to obtain functional recovery after SCI.

Original languageEnglish
Pages (from-to)1756-1770
Number of pages15
JournalMolecular Therapy
Volume26
Issue number7
DOIs
StatePublished - Jul 5 2018

Bibliographical note

Publisher Copyright:
© 2018

Keywords

  • anti-inflammatory cytokines
  • immunoengineering
  • lentiviral gene delivery
  • multichannel bridge
  • spinal cord injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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