hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation

Mater Sci Eng C Mater Biol Appl. 2018 Aug 1:89:194-204. doi: 10.1016/j.msec.2018.04.006. Epub 2018 Apr 10.

Abstract

The exploration of effective spinal cord injury (SCI) healing still remain a great challenge due to the high morbidity, complex pathology and unclear targets. Human umbilical cord mesenchymal stem cells (hucMSC) play an important role in tissue regeneration. However, transplanting stem cells has a potential risk of teratogenicity. Recent studies have suggested that exosomes secreted by stem cells may contribute to tissue injury repair. We hypothesized that the application of hucMSC derived exosomes may be a potential way for SCI treatment. Our studies showed the hucMSC derived exosomes with a mean particle size of 70 nm could effectively trigger the bone marrow derived macrophage (BMDM) polarization from M1 to a M2 phenotype. In vivo studies demonstrated that the hucMSC derived exosomes could improve the functional recovery after SCI through down-regulation of the inflammatory cytokines, such as TNF-α, MIP-1α, IL-6 and IFN-γ. Collectively, our findings indicated that hucMSC derived exosomes could facilitate spinal cord injury healing via attenuating the inflammation of the injury region. Our results provided a new perspective and therapeutic strategy for the use of hucMSC derived exosomes in soft tissue repair.

Keywords: Exosomes; Human umbilical cord mesenchymal stem cells; Inflammatory cytokines; Macrophage; Spinal cord injury.

MeSH terms

  • Animals
  • Arginase / metabolism
  • Cell Polarity / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Exosomes / metabolism
  • Exosomes / transplantation*
  • Female
  • Humans
  • Inflammation / prevention & control
  • Lipopolysaccharides / pharmacology
  • Locomotion
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / metabolism
  • Phenotype
  • Recovery of Function
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Spinal Cord Injuries / veterinary
  • Tetraspanin 30 / metabolism
  • Umbilical Cord / cytology

Substances

  • Cytokines
  • Lipopolysaccharides
  • Tetraspanin 30
  • Nitric Oxide Synthase Type II
  • Arg1 protein, mouse
  • Arginase