title: Concomitant differentiation of a population of mouse embryonic stem cells into neuron-like cells and schwann cell-like cells in a slow-flow microfluidic device.
abstract: To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining spiral ganglion neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived "neurons" could potentially substitute for lost or damaged SGN. mESC-derived "Schwann cells" produce MIF, as do all Schwann cells (Huang et al., a; Roth et al., 2007; Roth et al., 2008) and could attract SGN to a "cell-coated" implant.
  
  
  
  Neuron- and Schwann cell-like cells were produced from a common population of mESCs in an ultra-slow-flow microfluidic device. As the populations interacted, "neurons" grew over the "Schwann cell" lawn, and early events in myelination were documented. Blocking MIF on the Schwann cell side greatly reduced directional neurite outgrowth. MIF-expressing "Schwann cells" were used to coat a CI: Mouse SGN and MIF-induced "neurons" grew directionally to the CI and to a wild-type but not MIF-knockout organ of Corti explant.
  
  
  
  Two novel stem cell-based approaches for treating the problem of sensorineural hearing loss are described. Developmental Dynamics 246:7-27, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Poornapriya
authors.initials: P
authors.lastname: Ramamurthy
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: White
authors.affiliation: School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Joong
authors.initials: J
authors.lastname: Yull Park
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan.|Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Hume
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Ebisu
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Flor
authors.initials: F
authors.lastname: Mendez
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takayama
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.|Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kate F
authors.initials: KF
authors.lastname: Barald
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003054:Cochlear Implants / Q000592:standards; D034381:Hearing Loss / Q000628:therapy; D019746:Intramolecular Oxidoreductases / Q000502:physiology; D056656:Lab-On-A-Chip Devices / Q000592:standards*; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D012583:Schwann Cells / Q000166:cytology*; D013136:Spiral Ganglion
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
keywords: Schwann cells; cochlear implant; deafness; inner ear neurons; microfluidics; myelination; stem cells