Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats

Taotao Hu; Shusen Chang; Fang Qi; Zhonghui Zhang; Jiayin Chen; Lingli Jiang; Dali Wang; Chengliang Deng; Kaiyu Nie; Guangchao Xu; Zairong Wei

doi:10.1093/burnst/tkad013

Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats

Burns Trauma. 2023 Apr 27:11:tkad013. doi: 10.1093/burnst/tkad013. eCollection 2023.

Authors

Taotao Hu^{1

2}, Shusen Chang^{1

2}, Fang Qi^{1

2}, Zhonghui Zhang^{1

2}, Jiayin Chen^{1

2}, Lingli Jiang^{1

2}, Dali Wang^{1

2}, Chengliang Deng^{1

2}, Kaiyu Nie^{1

2}, Guangchao Xu^{1

2}, Zairong Wei^{1

2}

Affiliations

¹ Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China.
² The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, Guizhou, 563003, China.

Abstract

Background: Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration.

Methods: SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment.

Results: SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells.

Conclusions: These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.

Keywords: Exosomes; Mesenchymal stem cells; Nerve regeneration; Peripheral nerve injury; Schwann cell-like cells.