Effects of Different Doses of Mesenchymal Stem Cells on Functional Recovery After Compressive Spinal-Cord Injury in Mice

Neuroscience. 2019 Feb 21;400:17-32. doi: 10.1016/j.neuroscience.2018.12.005. Epub 2018 Dec 13.

Abstract

Despite advances in technology and rehabilitation, no effective therapies are available for patients with SCI, which remains a major medical challenge. This study compared the efficacy of 3 different doses of mesenchymal stem cells (MSCs) administered by intraperitoneal injection as a therapeutic strategy for compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal-cord compression for 1 min with a 30-g vascular clip. The animals received an intraperitoneal (i.p.) injection of MSCs (8 × 104, 8 × 105 or 8 × 106 in 500 μl) or DMEM (500 μl), one week after SCI. The cells of the three MSC doses administered i.p. were able to migrate to the injury site, increase local expression of trophic factors, and enhance fiber sparing and/or regeneration, accompanied by substantial improvement in locomotor performance. Cell transplantation at 8 × 105 density showed the best therapeutic potential, leading to significant tissue and functional improvements compared to the other two doses. These findings indicate that i.p. application of MSCs at the density of 8 × 105 yielded the best results, suggesting that this dose is a good choice for SCI treatment.

Keywords: compressive spinal cord inury; doses; intraperitoneal injection; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Female
  • Gliosis / etiology
  • Locomotion
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / physiology*
  • Mice, Inbred C57BL
  • Nerve Fibers, Myelinated / physiology
  • Neurotrophin 3 / metabolism
  • Recovery of Function*
  • Spinal Cord Compression / complications
  • Spinal Cord Compression / physiopathology*
  • Spinal Cord Compression / surgery*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Neurotrophin 3