Repair of spinal cord injury in rats via exosomes from bone mesenchymal stem cells requires sonic hedgehog

Yijia Jia; Jianwen Yang; Tingsheng Lu; Xingwei Pu; Qiling Chen; Linsong Ji; Chunshan Luo

doi:10.1016/j.reth.2021.08.007

Repair of spinal cord injury in rats via exosomes from bone mesenchymal stem cells requires sonic hedgehog

Regen Ther. 2021 Sep 1:18:309-315. doi: 10.1016/j.reth.2021.08.007. eCollection 2021 Dec.

Authors

Yijia Jia¹, Jianwen Yang¹, Tingsheng Lu¹, Xingwei Pu¹, Qiling Chen¹, Linsong Ji¹, Chunshan Luo¹

Affiliation

¹ Department of Spine Surgery, Guizhou Province Osteological Hospital, Guiyang, 550002, China.

Abstract

Objective: The loss of neural ability leading to subsequent diminishing of motor function and the impairment below the location of the injury is a result of the SCI (Spinal Cord Injury). Among the many therapeutic agents for SCI, the exosomes considered as extracellular vesicles seem to be the most promising. Sonic Hedgehog (Shh) is an exosome-carrying protein. This Study's purpose was to identify whether Shh is required for exosomes from BMSCs (mesenchymal stem cells of the bone) and plays a protective effect on SCI.

Methods: Spinal cord injection with shRNA Shh-adeno associated virus (sh-Shh-AAV) were used to silence Shh. Exosomes were extracted from BMSCs. Rats that had suffered SCI were given intravenous injections of exosomes through the veins of the tail. Immunohistochemistry was used to identify the expression of Shh glycoprotein molecule as well as the expression of Gli-1 (glioma-associated oncogene homolog 1) in the rat spinal cord tissues. Western blot was performed to measure the levels of growth associated protein-43 (GAP-43). The BBB (Basso Beattie Bresnahan) score was used to assess the motor functions of the hind legs. In the same manner, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or TUNEL and Nissl Staining was deployed to assess the level of regeneration of neurons and assess the level of histopathological damage in the tissues of the Spinal Cord.

Results: In the case of the rats with SCI, the levels of display of Gli-1 and Shh showed dramatic improvement after the BMSCs exosome injections. In comparison to rats with SCI, the subjects of BMSCs exosomes group showed an improvement in their SCI, including a higher BBB score and Nissl body count, increasing GAP-43 expression, along with a much-decreased number of cells that suffered apoptosis. While the exosome effect on Spinal Cord Injury was completely ineffective in rats that had Shh silencing.

Conclusions: Exosomes secreted from BMSCs showed great effectiveness in the SCI healing with a vital involvement of Shh in this repair.

Keywords: BMSCs; Exosomes; Sonic hedgehog; Spinal cord injury.