Transplantation of bone marrow mesenchymal stem cells alleviates spinal cord injury via inhibiting Notch signaling

Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):31-38. doi: 10.26355/eurrev_201908_18625.

Abstract

Objective: To analyze the mechanism of action by which the bone marrow mesenchymal stem cells (BMMSCs) repair the spinal cord injury (SCI) in rats via the Notch signaling pathway.

Materials and methods: A total of 75 male rats aged about 12 weeks old were equally divided into group A (sham operation group), group B (model group), and group C (model group + BMMSCs). The SCI model was established by Allen's method, and the differences in presenilin-1, Hes1 and Notch proteins among the three groups of rats were evaluated via immunohistochemical staining and Western blotting.

Results: Group B exhibited a lower Basso, Beattie, and Bresnahan (BBB) score at each time point than group A and group C (p<0.05), and the BBB score in group C was lower than that in group A (p<0.05). According to the average optical density analysis results of the immunohistochemically stained proteins, the optical density of presenilin-1 protein in group A was lower than that in both group B and group C (p<0.05), and group C exhibited a lower optical density of presenilin-1 protein than group B. In group A, the protein expression of Hes1 in the bone marrow tissues of rats was not evident and weakly positive. Compared with that in group A, it was substantially raised (p<0.05), and the strongly positively expressed Hes1 proteins were yellow or dark brown in group B. Compared with that in group B, the color of Hes1 proteins was lighter (p<0.05), and the positive level of Hes1 proteins was lowered in group C. Group A showed inconspicuously positively expressed Notch proteins, group B brown active Notch proteins, while group C several brown Notch proteins. The optical density of Notch proteins in group A was overtly lower than that in group B and group C (p<0.05), and it was significantly lower in group C than that in group B (p<0.05). Additionally, group B had an evidently higher expression level of Notch proteins than the other two groups (p<0.05), and the expression level of Notch proteins in group C was a little higher than that in group A (p<0.05).

Conclusions: BMMSCs inhibit the Notch signals to promote the proliferation and differentiation of rat neurons, thereby repairing spinal neurons.

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Presenilin-1 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / therapy*
  • Transcription Factor HES-1 / metabolism
  • Treatment Outcome

Substances

  • Hes1 protein, rat
  • Presenilin-1
  • Psen1 protein, rat
  • Receptors, Notch
  • Transcription Factor HES-1