The application of stem cells for regeneration of auditory sensory cells

Abstract: The cochlear sensory hair cells and auditory neurons are susceptible to a range of insults which causes their irreversible damage and loss, resulting in hearing loss. We are interested in the application of human pluripotent stem cells to reverse damage to these sensory cell types and thus preserve or restore hearing. This paper will describe two of our key research projects involving in vitro hair cell differentiation for disease modelling and in vivo application of stem cell-derived neurons to the deaf cochlea.  Recent experimentation deriving inner ear hair cells from organoids has illustrated that functional inner ear phenotypes can be produced in vitro. We have characterised these hair cell phenotypes using micro-CT, helium microscopy and patch clamp electrophysiology. The described model can be utilised to further interrogate normal hair cell development and differentiation, but also pathological hair cell function for disease modelling applications. In addition, we have developed a novel in vivo model to better quantify functional improvements when stem cell-derived sensory neurons are combined with cochlear implantation in the deaf mammalian cochlea. This new focal lesion model allows us to test the functional and tonotopic integration of stem cell-derived neurons into existing circuitry, thus addressing a critical step for all neural stem cell therapy more generally. Whilst currently in the basic research phase, our experimentation is designed to be directly applicable in the clinic, with an emphasis on providing patient-matched stem cells for either disease modelling or for surgical transplantation.

 

Biography: Bryony Nayagam undertook her PhD with Professor Rob Shepherd at the Bionic Ear Institute in Melbourne (2003-2006), where she examined the potential of stem cells to provide replacement neurons to the deaf mammalian cochlea. She went on to study with Prof Albert Edge (Eaton Peabody Lab, Boston) and Prof David Ryugo (Johns Hopkins University, Baltimore) as part of a Victoria Fellowship awarded in 2007. Bryony has been an Honorary Research Fellow at the Institute for the last 10 years and currently holds a Garnett Passe and Rodney Williams Memorial Foundation Research Fellowship. Her main interests lie in stem cell, gene and regenerative therapies for hearing restoration, with an emphasis on whether transplanted stem cells can rewire functional circuits.

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