Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations

Abstract

(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear.

Keywords: cochlea; cochlear implantation; exosomes; extracellular vesicles; hearing loss; inflammation; multipotent mesenchymal stromal cells; oxidative stress; umbilical cord.

Figure 1

Schematic flow of EV production for medicinal use in Neurotology. (1) Establishing the cell source for EV. (2) Cells release the EV 3 to the tissue culture media. (3) Collection of the conditioned medium. (4) EVs purification. (5) EVs characterization. (6) Clinical application of purified and characterized EVs for the inner ear conditions. Created with BioRender.com.