Directed Differentiation of Human Embryonic Stem Cells Toward Placode-Derived Spiral Ganglion-Like Sensory Neurons.
The ability to generate spiral ganglion neurons (SGNs) from stem cells is a necessary prerequisite for development of cell-replacement therapies for sensorineural hearing loss. We present a protocol that directs human embryonic stem cells (hESCs) toward a purified population of otic neuronal progenitors (ONPs) and SGN-like cells. Between 82% and 95% of these cells express SGN molecular markers, they preferentially extend neurites to the cochlear nucleus rather than nonauditory nuclei, and they generate action potentials. The protocol follows an in vitro stepwise recapitulation of developmental events inherent to normal differentiation of hESCs into SGNs, resulting in efficient sequential generation of nonneuronal ectoderm, preplacodal ectoderm, early prosensory ONPs, late ONPs, and cells with cellular and molecular characteristics of human SGNs. We thus describe the sequential signaling pathways that generate the early and later lineage species in the human SGN lineage, thereby better describing key developmental processes. The results indicate that our protocol generates cells that closely replicate the phenotypic characteristics of human SGNs, advancing the process of guiding hESCs to states serving inner-ear cell-replacement therapies and possible next-generation hybrid auditory prostheses. © Stem Cells Translational Medicine 2017;6:923-936.
['Matsuoka|Akihiro J|AJ|', 'Morrissey|Zachery D|ZD|', 'Zhang|Chaoying|C|', 'Homma|Kazuaki|K|', 'Belmadani|Abdelhak|A|', 'Miller|Charles A|CA|', 'Chadly|Duncan M|DM|', 'Kobayashi|Shun|S|', 'Edelbrock|Alexandra N|AN|', 'Tanaka-Matakatsu|Miho|M|', 'Whitlon|Donna S|DS|', 'Lyass|Ljuba|L|', 'McGuire|Tammy L|TL|', 'Stupp|Samuel I|SI|', 'Kessler|John A|JA|']
D000818:Animals D001933:Brain Stem D002454:Cell Differentiation D002460:Cell Line D019070:Cell Lineage D002465:Cell Movement D002470:Cell Survival D018920:Coculture Techniques D000066449:Human Embryonic Stem Cells D006801:Humans D051379:Mice D058953:Neural Stem Cells D051381:Rats D011984:Sensory Receptor Cells D013136:Spiral Ganglion
Embryonic stem cells Stem cell Cellular therapy Neural differentiation Neural induction Progenitor cells Transplantation