Hearing regeneration and regenerative medicine: present and future approaches

Abstract

More than 5% of the world population lives with a hearing impairment. The main factors responsible for hearing degeneration are ototoxic drugs, aging, continued exposure to excessive noise and infections. The pool of adult stem cells in the inner ear drops dramatically after birth, and therefore an endogenous cellular source for regeneration is absent. Hearing loss can emerge after the degeneration of different cochlear components, so there are multiple targets to be reached, such as hair cells (HCs), spiral ganglion neurons (SGNs), supporting cells (SCs) and ribbon synapses. Important discoveries in the hearing regeneration field have been reported regarding stem cell transplantation, migration and survival; genetic systems for cell fate monitoring; and stem cell differentiation to HCs, SGNs and SCs using adult stem cells, embryonic stem cells and induced pluripotent stem cells. Moreover, some molecular mediators that affect the establishment of functional synapses have been identified. In this review, we will focus on reporting the state of the art in the regenerative medicine field for hearing recovery. Stem cell research has enabled remarkable advances in regeneration, particularly in neuronal cells and synapses. Despite the progress achieved, there are certain issues that need a deeper development to improve the results already obtained, or to develop new approaches aiming for the clinical application.