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

Molecular Therapy : the Journal of the American Society of Gene Therapy
Jonghyuck ParkLonnie D Shea

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 secon...Continue Reading

Citations

Jul 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jonghyuck ParkLonnie D Shea
Dec 25, 2019·Current Molecular Medicine·Hong Zhang, Tao Yang
Apr 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ningning ChenFuxin Wei
Dec 20, 2018·Neurosurgery·Andrea A BrockJohn D Rolston
Jan 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andrea MastinuMaurizio Memo
Oct 15, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jessica Y ChenLonnie D Shea
May 28, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kufreobong E InyangGeoffroy Laumet
Dec 9, 2019·ACS Biomaterials Science & Engineering·Dominique R SmithLonnie D Shea
Dec 16, 2020·ACS Biomaterials Science & Engineering·Andrew J CicirielloCourtney M Dumont
Jan 16, 2021·ACS Biomaterials Science & Engineering·Zhe GongChengzhen Liang

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