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

摘要

Background: 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. Results: 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. Conclusions: Two novel stem cell-based approaches for treating the problem of sensorineural hearing loss are described. Developmental Dynamics 246:7-27, 2017. (c) 2016 Wiley Periodicals, Inc.