Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells

• Published in: Stem cell reports Vol. 14; no. 6; pp. 996 - 1008
• Main Authors: Tang, Pei-Ciao, Hashino, Eri, Nelson, Rick F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.06.2020; Elsevier
• Subjects: Animals; disease modeling; Ear, Inner - cytology; Ear, Inner - physiology; Hearing Loss, Sensorineural - therapy; Humans; inner ear; Neural Stem Cells - cytology; Neural Stem Cells - physiology; Neurogenesis; organoid; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - transplantation; Review; Stem Cell Transplantation - methods; stem cells; therapy; stem cells; inner ear; therapy; disease modeling; organoid
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2020.04.008

Sensorineural hearing loss and vestibular dysfunction are caused by damage to neurons and mechanosensitive hair cells, which do not regenerate to any clinically relevant extent in humans. Several protocols have been devised to direct pluripotent stem cells (PSCs) into inner ear hair cells and neurons, which display many properties of their native counterparts. The efficiency, reproducibility, and scalability of these protocols are enhanced by incorporating knowledge of inner ear development. Modeling human diseases in vitro through genetic manipulation of PSCs is already feasible, thereby permitting the elucidation of mechanistic understandings of a wide array of disease etiologies. Early studies on transplantation of PSC-derived otic progenitors have been successful in certain animal models, yet restoration of function and long-term cell survival remain unrealized. Through further research, PSC-based approaches will continue to revolutionize our understanding of inner ear biology and contribute to the development of therapeutic treatments for inner ear disorders. Tang and colleagues reviewed the use of pluripotent stem cells (PSCs) in the treatment and study of inner ear disorders. Precisely timed small-molecule treatments of PSCs generate inner ear hair cells, and support cells and neurons. Stem cell-based transplantation studies have shown successful engraftment in the inner ear and disease mechanisms can be studied in vitro using PSC-derived inner ear tissues.