Stem cell-derived exosome therapy for traumatic brain injury and its auditory complications

Traumatic brain injury poses substantial public health and socio-economic threat globally. Hearing loss is one of the most common sensory complications of TBI. Post-traumatic hearing handicap causes impairment in cognition and communication, which further reduce the quality of life of TBI patients. Treatment option for TBI and concurrent auditory complications are limited. Stem cell-derived exosome therapy has recently proven a versatile and potent treatment. After a meticulous dissection of relevant literature, we present this comprehensive, up-to-date, pathophysiology-specific and translation-oriented review to highlight the application and mechanism of stem cell-derived exosome therapy on TBI and its auditory complications. We first explored various epidemiological, clinical, and audiological traits connecting TBI and hearing loss. Then, multiple therapeutic effects of SC-Exos were demonstrated, such as the anti-inflammatory, anti-oxidative, anti-apoptotic, anti-excitotoxic, and neurotrophic potential. These effects precisely align with the main pathophysiological events contributing to TBI and hearing reduction, such as neuroinflammation, oxidative stress, programmed cell death, excitotoxicity, and neural degeneration. In addition, strategies to enhance the therapeutic effects, such as biomaterial-facilitated local delivery and internal and external exosomal modification, were showcased. Finally, we presented few pioneering clinical trials of using SC-Exos on human subjects with TBI and sensorineural hearing loss. In this review, we highlight stem cell-derived exosomes as promising treatment modality for TBI and its auditory complications. We recommend that future research extend wisdoms from this work to managing other sensory complications after TBI with possibilities of clinical translation.