Organotypic Cocultures of Human Pluripotent Stem Cell Derived- Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

dc.contributor.authorHyakumura, Tomoko
dc.contributor.authorMcDougall, Stuart
dc.contributor.authorFinch, Sue
dc.contributor.authorNeedham, Karina
dc.contributor.authorDottori, Mirella
dc.contributor.authorNayagam, Bryony
dc.date.accessioned2019-12-18T06:07:09Z
dc.date.available2019-12-18T06:07:09Z
dc.date.issued2019-12
dc.description.abstractStem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.en_US
dc.description.sponsorshipThis work was supported by the National Health and Medical Research Council of Australia (GNT 1023372 and 2012-2017 to B.A.N.), a Research Fellowship from the Garnett Passe and Rodney Williams Memorial Foundation (B.A.N.), the University of Melbourne, and graduate research scholarships from the Australian Stem Cell Centre and the Australian Government (Australian Post-Graduate Award, to T.H.). The Bionics Institute acknowledges the support it receives from the Victorian Government through its Operational Infrastructure Support Program.en_US
dc.identifier.citationHyakumura, T., S. McDougall, S. Finch, K. Needham, M. Dottori, and B. A. Nayagam. 2019. Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices. Stem Cells International. 2019: 8419493.en_US
dc.identifier.issn1687-966X (Print)
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/373
dc.language.isoenen_US
dc.publisherHindawien_US
dc.titleOrganotypic Cocultures of Human Pluripotent Stem Cell Derived- Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slicesen_US
dc.typeArticleen_US
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