Schwann Cell-Derived Exosomes Ameliorate Paclitaxel-Induced Peripheral Neuropathy Through the miR-21-Mediated PTEN Signaling Pathway

Abstract

Paclitaxel-induced peripheral neuropathy (PIPN) is a neurological disorder resulting from paclitaxel (PTX) treatment for cancer patients. There are currently no drugs available that can definitively prevent or treat PIPN. Exosomes are cell-secreted nanoscale vesicles that mediate communication between neurons and glial cells. We found that Schwann cell-derived exosomes (SC-EXOs) robustly improved PIPN both in vitro and in vivo. In vivo studies showed that SC-EXOs were able to alleviate PTX-induced mechanical nociceptive sensitization in rats. Pathomorphological analysis showed that SC-EXOs ameliorated PTX-induced plantar intraepidermal nerve fiber loss and dorsal root ganglion (DRG) injury. Additionally, the results of in vitro studies showed that SC-EXOs had significant protective effects on the DRG cells damaged by PTX, and did not affect the antitumor effect of PTX against Hela cells. Further, mechanism research revealed that SC-EXOs promoted axonal regeneration and protected damaged neurons by upregulating miR-21 to repress the phosphatase and tensin homolog (PTEN) pathway, which could improve PIPN. Taken together, these findings suggest that SC-EXOs ameliorate PTX-induced peripheral neuropathy via the miR-21-mediated PTEN signaling pathway, which provides a novel strategy for the treatment of PIPN.

Keywords: Axon; Exosomes; Paclitaxel; Peripheral nerve; Schwann cells.