The use of animal models to study cell transplantation in neuropathic hearing loss

Abstract

Auditory neuropathy (AN) is a form of sensorineural deafness specifically affecting the conduction of the nerve impulse from the cochlear hair cells to the auditory centres of the brain. As such, the condition is a potential clinical target for 'cell replacement therapy', in which a functioning auditory nerve is regenerated by transplanting an appropriated neural progenitor. In this review, we survey the current literature and examine possible experimental models for this condition, with particular reference to their compatibility as suitable hosts for transplantation. The use of exogenous neurotoxic agents such as ouabain or β-bungarotoxin is discussed, as are ageing and noise-induced synaptopathy models. Lesioning of the nerve by mechanical damage during surgery and the neuropathy resulting from infectious diseases may be very relevant clinically, and we discuss whether there are good models for these situations. We also address genetic models for AN, examining whether the phenotypes truly model the clinical situation in their human counterpart syndromes-we use the example of the hyperbilirubinaemic Gunn rat as a particular instance in this regard.

Directed differentiation and direct reprogramming: Applying stem cell technologies to hearing research

“…In vivo environmental factors have been shown to substantially improve cell specification 122 and tissue maturation upon in situ transdifferentiation 178 or transplantation, 59 suggesting that the local niche signals may enhance reprogramming compared to in vitro. Adapting preclinical animal models developed for cell replacement strategies through transplantation 180 to probe in situ reprogramming may enable to test whether the generation of glutamatergic neurons with proper peripheral and central connection may suffice to relay acoustic or electrical signals.…”

“…Adapting preclinical animal models developed for cell replacement strategies through transplantation 180 to probe in situ reprogramming may enable to test whether the generation of glutamatergic neurons…”

Inner ear organoids: new tools to understand neurosensory cell development, degeneration and regeneration

“…However, the incomplete differentiation of the organ of Corti at early stages can result in a response that differs between young postnatal animals and adults, because of the higher regenerative potential and differences in sensitivity of neonates to ototoxic agents (Henley and Rybak, 1995). Alternatively, toxicity and regeneration can be studied directly in vivo, using animal models in which hearing thresholds or sensory cell survival can be tested (Abbas and Rivolta, 2015;Abbas and Rivolta, 2019;Breglio et al, 2017;Furman et al, 2013;Kujawa and Liberman, 2019). The level of complexity of animal testing using rodents is substantial, and as only a small number of compounds or concentrations can be handled simultaneously, these experiments are difficult to scale up to medium-or high-throughput screens.…”

“…Transplantation of PSC-derived (otic) neuronal progenitor cells into the modiolus/nerve trunk has been advancing in preclinical models and is a viable option to repopulate the spiral ganglion after cell loss resulting from neuropathies (Chen et al, 2012;Corrales et al, 2006;Shi et al, 2007). This approach could increase the effectiveness of neuroprosthetic stimulation in cochlear implant recipients (Abbas and Rivolta, 2019). Whether spiral ganglion neuron progenitors derived using the latest 3D induction protocol would lead to improved functional outcomes remains to be tested.…”

Genetics and Acquired Hearing Loss

“…Moza Al-Kowari* and Meritxell Espino-Guarch Translational Medicine, Sidra Medicine Hospital, Doha, Qatar *Address all correspondence to: malkowari@sidra.org the in-depth study of stem cell and its therapeutic potential, stem cell technology opened new approaches for hair cell and auditory nerve regeneration [137,138]. By using two strategies of endogenous stem cell activation and exogenous stem cell transplantation, exciting results on restoring hearing function are showed.…”