MSC-sEV Promote Regeneration of Cochlear Spiral Ganglion Neurons and Myelin Sheaths in 3D Culture System
Yunyou You1,2,3 · Anning Chen1,2,3 · Jiaxi Qu1,2,3 · Yiman Guo4 · Jing Pan1,2,3 · Taolue Yu1,2,3 · Fan Shu1,2,3 · Jie Tang1,2,3,5,6 · Hongzheng Zhang1,2,3
1 Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
2 Ear Research Institute, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
3 Institute for Brain Science and Intelligence, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
4 The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
5 Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
6 Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou 510515, China
Abstract
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.
Keywords
Spiral ganglion neuron; Schwann cells; Mesenchymal stem cells; Small extracellular vesicles; Regeneration
