Directed differentiation of human embryonic stem cells toward placode-derived spiral ganglion-like sensory neurons

Akihiro J. Matsuoka, Zachery D. Morrissey, Chaoying Zhang, Kazuaki Homma, Abdelhak Belmadani, Charles A. Miller, Duncan M. Chadly, Shun Kobayashi, Alexandra N. Edelbrock, Miho Tanaka-Matakatsu, Donna S. Whitlon, Ljuba Lyass, Tammy L. McGuire, Samuel I. Stupp, John A. Kessler

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)923-936
Number of pages14
JournalStem Cells Translational Medicine
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 2017

Keywords

  • Cellular therapy
  • Embryonic stem cells
  • Neural differentiation
  • Neural induction
  • Progenitor cells
  • Stem cell
  • Transplantation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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  • Cite this

    Matsuoka, A. J., Morrissey, Z. D., Zhang, C., Homma, K., Belmadani, A., Miller, C. A., Chadly, D. M., Kobayashi, S., Edelbrock, A. N., Tanaka-Matakatsu, M., Whitlon, D. S., Lyass, L., McGuire, T. L., Stupp, S. I., & Kessler, J. A. (2017). Directed differentiation of human embryonic stem cells toward placode-derived spiral ganglion-like sensory neurons. Stem Cells Translational Medicine, 6(3), 923-936. https://doi.org/10.1002/sctm.16-0032