The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury

Gentaro Kumagai, W. Dalton Dietrich

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting experimental and clinical spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75NTR receptors or MSC-MNTS1p75<sup>-</sup> that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP, or MSC-MNTS1/p75<sup>-</sup>/GFP was delivered into the injury epicenter. All transplanted groups showed reduced inflammation and cystic cavity size compared to control SCI rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75<sup>-</sup>, but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75<sup>-</sup> promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor-dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI.

Original languageEnglish (US)
Title of host publicationNeuroprotection and Regeneration of the Spinal Cord
PublisherSpringer Japan
Pages255-268
Number of pages14
Volume9784431545026
ISBN (Print)9784431545026, 4431545018, 9784431545019
DOIs
StatePublished - Nov 1 2013

Fingerprint

Stromal Cells
Mesenchymal Stromal Cells
Spinal Cord Injuries
Bone Marrow
Transplantation
trkC Receptor
Nerve Growth Factor Receptors
Investigational Therapies
Aptitude
Nerve Growth Factors
Growth
Neuroglia
Cicatrix
Hypersensitivity
Anti-Inflammatory Agents
Inflammation
Skin

Keywords

  • Axonal regeneration
  • Multineurotrophin
  • Rat bone marrow stromal cells
  • Spinal cord injury
  • Transplantation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kumagai, G., & Dalton Dietrich, W. (2013). The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. In Neuroprotection and Regeneration of the Spinal Cord (Vol. 9784431545026, pp. 255-268). Springer Japan. https://doi.org/10.1007/978-4-431-54502-6_21

The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. / Kumagai, Gentaro; Dalton Dietrich, W.

Neuroprotection and Regeneration of the Spinal Cord. Vol. 9784431545026 Springer Japan, 2013. p. 255-268.

Research output: Chapter in Book/Report/Conference proceedingChapter

Kumagai, G & Dalton Dietrich, W 2013, The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. in Neuroprotection and Regeneration of the Spinal Cord. vol. 9784431545026, Springer Japan, pp. 255-268. https://doi.org/10.1007/978-4-431-54502-6_21
Kumagai G, Dalton Dietrich W. The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. In Neuroprotection and Regeneration of the Spinal Cord. Vol. 9784431545026. Springer Japan. 2013. p. 255-268 https://doi.org/10.1007/978-4-431-54502-6_21
Kumagai, Gentaro ; Dalton Dietrich, W. / The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. Neuroprotection and Regeneration of the Spinal Cord. Vol. 9784431545026 Springer Japan, 2013. pp. 255-268
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