Poornapriya Ramamurthy1,2, Joshua B White1, Joong Yull Park3, Richard I Hume4,5, Fumi Ebisu2, Flor Mendez2, Shuichi Takayama1, Kate F Barald1,2,5. 1. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan. 2. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan. 3. School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, Republic of Korea. 4. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan. 5. Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.
Abstract
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.
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.
Authors: Jessica O Winter; Mrudula Gokhale; Ralph J Jensen; Stuart F Cogan; Joseph F Rizzo Journal: Mater Sci Eng C Mater Biol Appl Date: 2008-04-01 Impact factor: 7.328
Authors: Therese M Roth; Poornapriya Ramamurthy; Fumi Ebisu; Robert P Lisak; Beverly M Bealmear; Kate F Barald Journal: Glia Date: 2007-08-15 Impact factor: 7.452
Authors: Jeannie H Reyes; K Sue O'Shea; Noel L Wys; J Matthew Velkey; Diane M Prieskorn; Karolina Wesolowski; Josef M Miller; Richard A Altschuler Journal: J Neurosci Date: 2008-11-26 Impact factor: 6.167