> Despite the progress in our approach to achieve HC regeneration in the adult cochlea in vitro and in vivo, major challenges remain before potential clinical applications. First, regenerated HCs need to be terminally differentiated and fully mature, and to be located in the sensory epithelial region such that their stereocilia contact the tectorial membrane to mediate the mechanoelectrical transduction, as well as be able to survive long term. The current regenerated HC-like cells are immature and the time frame we used is not ideal to determine their long-term survival. One potential reason for the lack of terminal differentiation is the continuous Atoh1 expression mediated by adenovirus, which is known to impact HC maturation and is detrimental to HC survival (9, 56). Future studies to express Atoh1 transiently in the reprogrammed SCs could address the issue. Second, the surgical procedure of “cochleostomy” in the adult cochlea severely damages the microenvironment of the cochlea including extensive OHC death around the injection site. Future studies using an alternative delivery vehicle with a minimally invasive surgical procedure such as an AAV with round window injection could significantly improve HC regeneration efficiency without causing trauma to the inner ear. Third, major efforts should be made to identify/create new AAVs or novel delivery vehicles such as nanoparticles capable of targeting adult cochlear SCs for reprogramming. Finally, the restoration of hearing in adult deaf animal models significantly and reliably by HC regeneration will elevate the field of HC regeneration to a clinically relevant stage.
It sounds like the authors have found a more effective way to trigger generation of immature Hair Cells than was already known, but they're several large steps away from "restoration of hearing in adult deaf animal models".
However, the submitted article (from hms.harvard.edu) summarizes the findings as:
> [Authors] reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear.
While it's not outright false, the "successfully regenerated" isn't the way I'd interpret the PNAS paper. Perhaps I misread the paper.
Thanks for adding this context. As someone suffering from SNHL with a great wish to have some of my hearing restored, headlines & articles like these often give my a sense of hope for a near-term solution that turns out to be false. I wish (pop)scientific news would be a little bit more nuanced/careful..
Anyway, great that another small but significant step is made in this terribly complicated problem :)
Same here - suffering from Sensorineural hearing loss since I was a kid. Lots of hope but not seen a ubiquitous or even an experimental solution in sight.
> Despite the progress in our approach to achieve HC regeneration in the adult cochlea in vitro and in vivo, major challenges remain before potential clinical applications. First, regenerated HCs need to be terminally differentiated and fully mature, and to be located in the sensory epithelial region such that their stereocilia contact the tectorial membrane to mediate the mechanoelectrical transduction, as well as be able to survive long term. The current regenerated HC-like cells are immature and the time frame we used is not ideal to determine their long-term survival. One potential reason for the lack of terminal differentiation is the continuous Atoh1 expression mediated by adenovirus, which is known to impact HC maturation and is detrimental to HC survival (9, 56). Future studies to express Atoh1 transiently in the reprogrammed SCs could address the issue. Second, the surgical procedure of “cochleostomy” in the adult cochlea severely damages the microenvironment of the cochlea including extensive OHC death around the injection site. Future studies using an alternative delivery vehicle with a minimally invasive surgical procedure such as an AAV with round window injection could significantly improve HC regeneration efficiency without causing trauma to the inner ear. Third, major efforts should be made to identify/create new AAVs or novel delivery vehicles such as nanoparticles capable of targeting adult cochlear SCs for reprogramming. Finally, the restoration of hearing in adult deaf animal models significantly and reliably by HC regeneration will elevate the field of HC regeneration to a clinically relevant stage.
It sounds like the authors have found a more effective way to trigger generation of immature Hair Cells than was already known, but they're several large steps away from "restoration of hearing in adult deaf animal models".
However, the submitted article (from hms.harvard.edu) summarizes the findings as:
> [Authors] reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear.
While it's not outright false, the "successfully regenerated" isn't the way I'd interpret the PNAS paper. Perhaps I misread the paper.
[0] https://www.pnas.org/doi/10.1073/pnas.2215253120