Concomitant use of mesenchymal stem cells and neural stem cells for treatment of spinal cord injury: A combo cell therapy approach

Neurosci Lett. 2018 Mar 6:668:138-146. doi: 10.1016/j.neulet.2018.01.008. Epub 2018 Jan 6.

Abstract

with neural stem cells (NSCs) provides a hope to recover the neural damage and compensate for the lost neural structures for restoration of interrupted neural communications above and below the site of injury. However, cell-based therapy approach suffers from many biological barriers and technical caveats which severely hamper the prognosis. The biochemically-rich microenvironment at the site of spinal cord injury (SCI), the continuing neuro-degenerative process and infiltrating immune cells offer a serious barrier to the donor cells. We hypothesized that mesenchymal stem cells (MSCs) concomitantly delivered with NSCs would significantly enhance the effectiveness of cell-based therapy for SCI. In a rodent model of SCI (n = 15 animals/group), MSCs labeled with PKH67 (green fluorescence dye) were delivered on day1 after SCI whereas the same animals were treated with NSCs during the subacute phase on day3 (group-5). In comparison with untreated control (group-1), sham group (without cell treatment; group-2), MSCs alone (group-3) and NSCs alone treated animals (group-4), the combined cell treated animals (group-5) showed significantly higher homing of cells at the site of injury during in vivo imaging. Caspase-3 activity was lower in group-5 (P < 0.05 vs all groups) with concomitant reduction in the pro-inflammatory cytokines IL-1β and IL-6 (P < 0.05 vs all groups). All cell therapy groups showed significant improvement in neurological function as compared to group-2, however, it was highest in group-5 (P < 0.05 vs all groups). In conclusion, combined treatment with (NSCs + MSCs) enhances NSCs survival and functional recovery in SCI and is superior to the treatment with either of NSCs or MSCs alone.

Keywords: Cell therapy; Mesenchymal stem cell; Neural stem cell; Spinal cord injury; Stem cell; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells*
  • Neural Stem Cells / transplantation*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation / methods*