Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions
Abstract
:1. Introduction
2. Hearing Loss and Its Pathophysiology
2.1. Age-Related Hearing Loss
2.2. Noise-Induced Hearing Loss
2.3. Ototoxicity
3. Cochlear Development and Its Associated Pathways
3.1. Hair Cell Differentiation
3.1.1. Wnt and Notch Signaling
3.1.2. Sonic Hedgehog (Shh) Signaling
3.1.3. Fibroblast Growth Factor (FGF) Signaling
3.1.4. Bone Morphogenetic Protein (BMP) and Tissue Growth Factor β (TGFβ) Signaling
3.1.5. The Role of Micro-RNAs in Cochlear Development
3.2. Spiral Ganglion Neuron Differentiation
4. Target Cells for Potential Regenerative Treatment
5. Regenerative Potential of the Cochlea
5.1. Non-Mammalian Vertebrates
5.2. Neonatal Mammalian Cochlea
5.3. Adult Mammalian Cochlea
5.4. Epigenetic Barrier to Hair Cell Regeneration in Adult Cochlea
6. Promoting Regeneration & Re-Innervation
6.1. Manipulating a Single Signaling Pathway
6.2. Combined Strategies
6.3. Improving Functional Outcomes: Inner Hair Cell Re-Innervation after Cochlear Trauma
7. Human Inner Ear Regeneration and Clinical Trials Targeting Endogenous Stem Cells
8. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gene/ Protein | Species | Stage | Location in Cochlea per Stage | References |
---|---|---|---|---|
EpCAM | Mouse | Mature adult | RM, Cochlear HCs, SCs | [116] |
Human | Fetal | Chochlear duct | [115,116] | |
Lfng | Mouse | Postnatal | DC3 | [101] |
Mature adult | IphC, IPC, OPC, DC | [113] | ||
Lgr4 | Mouse | Embryonic | Cochlear duct and SGN | [23] |
Postnatal | DCs and IPCs | [23] | ||
Adolescent | DCs | [23] | ||
Lgr5 | Mouse | Embryonic | DC3, IPCs, IphCs, and the lateral GER | [22,82] |
Postnatal | IPC, GER, DC3, IPHC | [20,22,77,82,122] | ||
Adolescent | IPCs, DC3, IBC | [82,110] | ||
Mature adult | DC3, IPCs | [22,110] | ||
Deafened (p30) | Survival in DC3 only | [110] | ||
Human * | Fetal | Prosensory doman, LER, SCs | [115] | |
Lgr6 | Mouse | Embryonic | IPCs | [20] |
Postnatal | IPCs, IBCs (disappears at p30) | [20,22] | ||
Sox2 | Mouse | Embryonic | HCs, adjacent supporting cells and GER | [20,120] |
Postnatal | SCs | [22,82] | ||
Mature adult | BCs, IphCs, IPC, OPC, DCs, HeCs | [21,121] | ||
Deafened (p120) | BCs, IphCs, IPC, OPC, DCs, HeCs | [21,121] | ||
Human | Fetal | Organ of Corti | [115] |
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Smith-Cortinez, N.; Tan, A.K.; Stokroos, R.J.; Versnel, H.; Straatman, L.V. Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions. Int. J. Mol. Sci. 2023, 24, 7840. https://doi.org/10.3390/ijms24097840
Smith-Cortinez N, Tan AK, Stokroos RJ, Versnel H, Straatman LV. Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions. International Journal of Molecular Sciences. 2023; 24(9):7840. https://doi.org/10.3390/ijms24097840
Chicago/Turabian StyleSmith-Cortinez, Natalia, A. Katherine Tan, Robert J. Stokroos, Huib Versnel, and Louise V. Straatman. 2023. "Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions" International Journal of Molecular Sciences 24, no. 9: 7840. https://doi.org/10.3390/ijms24097840