Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury

Gentaro Kumagai, Pantelis Tsoulfas, Satoshi Toh, Ian McNiece, Helen M. Bramlett, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting 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-MNTS1/p75- that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP or MSC-MNTS1/p75-/GFP were 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-, but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75- 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)
Pages (from-to)369-380
Number of pages12
JournalExperimental neurology
Volume248
DOIs
StatePublished - Oct 2013

Keywords

  • Axonal regeneration
  • Functional recovery
  • MNTS1
  • P75
  • Rat bone marrow stromal cells
  • Spinal cord injury
  • Transplantation
  • Viral vector transduction

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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