MSC-sEV Promote Regeneration of Cochlear Spiral Ganglion Neurons and Myelin Sheaths in 3D Culture System.

Spiral ganglion neurons (SGNs) play a crucial role in auditory signal transmission, and their degeneration is a significant factor in hearing loss. The protection of SGNs remains a central focus in auditory neuropathy treatment, while repairing their surrounding myelin sheaths has often been underestimated. To better simulate the cochlear neural microenvironment and enhance regenerative therapy, we developed a regenerative strategy using mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) combined with a biomimetic 3D cochlear culture system. Our results demonstrate that MSC-sEV significantly promotes Schwann cell migration and proliferation, thereby supporting the structural integrity and trophic environment essential for SGN function. Simultaneously, MSC-sEV treatment markedly enhances SGN survival, axonal outgrowth, and neural network reconstruction within the 3D culture model, mimicking the in vivo cochlear microenvironment. Importantly, in an ouabain-induced auditory neuropathy model, MSC-sEV administration attenuated neuronal loss, preserved SGN-hair cell connectivity, and facilitated functional recovery. By targeting both SGNs and their myelin sheaths, this dual-action strategy effectively reconstructs the neuroglial functional unit, fostering a regenerative microenvironment for auditory circuit repair.