Research on GM1 bound bMSCs loaded with SF hydrogel for spinal cord injury repair.

BACKGROUND

Monosialotetrahexosylganglioside (GM1), a major ganglioside component, is expressed in the spinal cords of mammals. Gangliosides have been shown to play important roles in various physiological processes, including neuronal protection, neurorepair, and stem cell differentiation. Bone marrow-derived mesenchymal stem cells (bMSCs) were expected to be a good source of cells for clinical transplantation and repair due to their abundance, easy accessibility and lack of ethical restrictions. They can also be induced to differentiate into neurons. However, there is still no ideal delivery material or method that allows the sustained and controlled release of GM1 and bMSCs for clinical use in spinal cord injury (SCI). Silk fibroin (SF)-based hydrogels have emerged as a promising strategy for local, controlled, and sustained drug release in the treatment of various diseases.

METHODS

In this study, we developed a SF-based hydrogel for the sustained delivery of GM1 and bMSCs (GM1 + bMSCs@SF hydrogel) and evaluated its therapeutic effect in a rat model of SCI.

RESULTS

The GM1 + bMSCs@SF hydrogel showed sustained GM1 release in vitro. Treatment with the GM1 + bMSCs@SF hydrogel increased cell cycle exit and neuronal differentiation 1 (Cend1) expression, reduced neuronal pyroptosis and apoptosis, and promoted the differentiation of bMSCs into neurons. Double immunofluorescence staining confirmed a decrease in cell pyroptosis. Moreover, rats treated with the GM1 + bMSCs@SF hydrogel showed significant improvement in motor function recovery, with the Basso, Beattie and Bresnahan (BBB) score at 8 weeks reaching about 71.4% of the normal level, compared with about 30% in the SCI group.

CONCLUSIONS

This study will minimize neuronal damage by innovatively using SF hydrogel loaded with GM1 and bMSCs for spinal cord injury repair. It will also explore the molecular mechanisms underlying post-traumatic spinal cord injury repair, opening new therapeutic avenues for spinal cord injury treatment.