Learning Objectives: To present the current advances produced in our laboratory of the application of human pluripotent stem cells in the treatment of hearing loss.
The manipulation of human embryonic stem cells has open new horizons for regenerative medicine, especially for incurable conditions like deafness. Hopes have been fuelled further by the potential to generate patient-specific, induced-pluripotent stem cells (iPSCs).
Pluripotent stem cells need to be driven into the desired cell lineages. In our laboratory, we initially tackled this problem by isolating stem cells from the human fetal cochlea, and used them to unravel the basic signals involved in producing sensory cells. We then developed a method to generate otic cells from human embryonic stem cells (hESCs) using molecules that induce the formation of the ear in vivo. In this way we generated otic progenitors that can produce sensory hair cell-like cells and auditory neurons. When hESC-derived otic progenitors were transplanted into an animal model of auditory neuropathy, they survived, engrafted and differentiated into neurons. Moreover, they connected with the hair cells and the brain and, more remarkably, they elicited a functional recovery represented by improved ABR thresholds. We are now exploring if hESC-derived auditory neurons could interact with experimental cochlear implants. We have also developed iPSC lines using different techniques and we are adapting the methods developed for hESC for their use with iPSCs.
The field is still at an early stage, but the progress already achieved is substantial. Although the use of stem cells for hearing loss is likely to be initially limited to some conditions, this will probably change with the development of more efficient ways of producing sensory cells and with the improvement of delivery and grafting techniques. In summary, the presentation will revise the recent advances produced by our laboratory and the impact that this new technology could have in the future ways we treat this condition.
