scholarly journals Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids

2021 ◽  
Author(s):  
Daniel R. Romano ◽  
Eri Hashino ◽  
Rick F. Nelson
Keyword(s):  
Animal Models ◽  
Inner Ear ◽  
Auditory System ◽  
Hearing Aids ◽  
Molecular Mechanisms ◽  
Functional Disability ◽  
Experimental Studies ◽  
Hereditary Deafness ◽  
Human Auditory System ◽  
Human Inner Ear

AbstractSensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.

scholarly journals Navigating Hereditary Hearing Loss: Pathology of the Inner Ear

2021 ◽  
Vol 15 ◽  
Author(s):  
Teresa Nicolson
Keyword(s):  
Hearing Loss ◽  
Animal Models ◽  
Inner Ear ◽  
Auditory System ◽  
Cranial Nerve ◽  
Hereditary Hearing Loss ◽  
Hearing Organ ◽  
Peripheral Auditory System ◽  
The Brain

Inherited forms of deafness account for a sizable portion of hearing loss among children and adult populations. Many patients with sensorineural deficits have pathological manifestations in the peripheral auditory system, the inner ear. Within the hearing organ, the cochlea, most of the genetic forms of hearing loss involve defects in sensory detection and to some extent, signaling to the brain via the auditory cranial nerve. This review focuses on peripheral forms of hereditary hearing loss and how these impairments can be studied in diverse animal models or patient-derived cells with the ultimate goal of using the knowledge gained to understand the underlying biology and treat hearing loss.

scholarly journals Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Minjin Jeong ◽  
Karen E. Ocwieja ◽  
Dongjun Han ◽  
P. Ashley Wackym ◽  
Yichen Zhang ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
In Vitro Models ◽  
Cellular Models ◽  
Induced Pluripotent ◽  
Human Inner Ear

Abstract Background COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated with COVID-19 and molecular mechanisms underlying these deficits are incompletely understood. Methods We report a series of ten COVID-19 patients with audiovestibular symptoms such as hearing loss, vestibular dysfunction and tinnitus. To investigate the causal relationship between SARS-CoV-2 and audiovestibular dysfunction, we examine human inner ear tissue, human inner ear in vitro cellular models, and mouse inner ear tissue. Results We demonstrate that adult human inner ear tissue co-expresses the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2 virus, and the transmembrane protease serine 2 (TMPRSS2) and FURIN cofactors required for virus entry. Furthermore, hair cells and Schwann cells in explanted human vestibular tissue can be infected by SARS-CoV-2, as demonstrated by confocal microscopy. We establish three human induced pluripotent stem cell (hiPSC)-derived in vitro models of the inner ear for infection: two-dimensional otic prosensory cells (OPCs) and Schwann cell precursors (SCPs), and three-dimensional inner ear organoids. Both OPCs and SCPs express ACE2, TMPRSS2, and FURIN, with lower ACE2 and FURIN expression in SCPs. OPCs are permissive to SARS-CoV-2 infection; lower infection rates exist in isogenic SCPs. The inner ear organoids show that hair cells express ACE2 and are targets for SARS-CoV-2. Conclusions Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.

scholarly journals Possibility of using embryonic neural cells to regenerate structures of the inner ear of Guinea pigs after experimental ototoxicosis

2021 ◽  
Vol 16 (2) ◽  
pp. 178-183
Author(s):  
Iryna Ihorivna SAPIZHAK ◽  
◽  
V. PYSANKO ◽  
T. MALYSHEVA ◽  
◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Auditory Nerve ◽  
Guinea Pigs ◽  
Experimental Studies ◽  
Sensorineural Hearing ◽  
Neuronal Stem Cell ◽  
Morphological State

Hearing disorders greatly impair the comfort of life, change a person's emotional state, and when developed in early childhood lead to disorders of psycho-social formation of personality. There are currently no effective treatments for patients with sensorineural hearing loss (SNHL). Therefore, all over the world prefer "substitution tactics", namely - hearing aids for deafness, or cochlear implant for deafness. Aim. To evaluate the influence of NEC in different ways of their introduction on the morphological state of the structures of the inner ear (Corti's organ and the first neuron, vascular strip), as well as the auditory nerve on the background of aminoglycoside ototoxicosis. To investigate the characteristics and directions of reorganization of hemoblood supply and features of cyto - and myeloarchitectonics of structures of the inner ear. Materials and methods. To study the effectiveness of neuronal embryonic cells (NEC) in aminoglycoside ototoxicosis, experimental studies were performed on 40 guinea pigs weighing from 500 to 600 g. SNHL was caused by the introduction of aminoglycoside antibiotic - gentamicin sulfate at a dose of 100 mg/kg for 14 days. The neuronal stem cell suspension was administered in a volume of 2 million cells in 0.5 ml intratympanically and 2 million cells in 0.5 ml suboccipitally on days 1 and 15 of the experiment. Results and discussion. The influence of NEC on different methods of their introduction on the morphological state of the structures of the inner ear (Corti's organ and the first neuron), as well as the auditory nerve on the background of aminoglycoside ototoxicosis was evaluated. The characteristics and directions of reorganization of hemoblood supply and features of cyto - and myeloarchitectonics of structures of an inner ear according to an estimation of neurovasal relations are investigated. Conclusions. The data obtained indicate that intratympanic and suboccipital administration of NEC promotes the regeneration of damaged cell structures of the inner ear. This opens the prospect of using NEC to develop new approaches in the treatment of patients with sensorineural hearing loss.

A Neuro-Fuzzy Model for Simulating Outer Hair Cell of Human Cochlea

2005 ◽  
Author(s):  
Balaje T. Thumati ◽  
D. Subbaram Naidu ◽  
Larry Stout
Keyword(s):  
Neural Network ◽  
Fuzzy Logic ◽  
Hair Cell ◽  
Inner Ear ◽  
Auditory System ◽  
Outer Hair Cell ◽  
Basilar Membrane ◽  
Fuzzy Model ◽  
Feed Forward Neural Network ◽  
Human Auditory System

Understanding the functioning of the human auditory system has been of interest for decades and many mathematical models have been developed based on experimental results. Many of these models address the key components of the human auditory system: outer ear, middle ear, and inner ear, which consists of cochlea and organ of corti. In this paper, a novel approach for human auditory model is developed that is based on the concepts of fuzzy logic for simulating basilar membrane and stereocilia, and a feed-forward neural network for simulating outer hair cell of the inner ear. Frequency, intensity and the direction of stereocilia movement are the three inputs to the fuzzy logic portion of the model. The output of this block is the net force, which becomes the input to the neural network. The implementation and simulated results using MATLAB® are presented.

scholarly journals Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges

2020 ◽  
Vol 9 (7) ◽  
pp. 2309 ◽  
Author(s):  
Sedigheh Delmaghani ◽  
Aziz El-Amraoui
Keyword(s):  
Animal Models ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Age Groups ◽  
Sensorineural Deafness ◽  
The Elderly ◽  
Acoustic Trauma ◽  
Hearing Sensitivity ◽  
New Therapeutic Approaches

Hearing impairment is the most frequent sensory deficit in humans of all age groups, from children (1/500) to the elderly (more than 50% of the over-75 s). Over 50% of congenital deafness are hereditary in nature. The other major causes of deafness, which also may have genetic predisposition, are aging, acoustic trauma, ototoxic drugs such as aminoglycosides, and noise exposure. Over the last two decades, the study of inherited deafness forms and related animal models has been instrumental in deciphering the molecular, cellular, and physiological mechanisms of disease. However, there is still no curative treatment for sensorineural deafness. Hearing loss is currently palliated by rehabilitation methods: conventional hearing aids, and for more severe forms, cochlear implants. Efforts are continuing to improve these devices to help users to understand speech in noisy environments and to appreciate music. However, neither approach can mediate a full recovery of hearing sensitivity and/or restoration of the native inner ear sensory epithelia. New therapeutic approaches based on gene transfer and gene editing tools are being developed in animal models. In this review, we focus on the successful restoration of auditory and vestibular functions in certain inner ear conditions, paving the way for future clinical applications.

New possibility for measuring the cortical auditory evoked potentials: the HEARLab

2014 ◽  
Vol 155 (38) ◽  
pp. 1524-1529
Author(s):  
Ádám Bach ◽  
Ferenc Tóth ◽  
Vera Matievics ◽  
József Géza Kiss ◽  
József Jóri ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Evoked Potentials ◽  
Auditory System ◽  
Hearing Aids ◽  
Pure Tone ◽  
Auditory Evoked Potentials ◽  
Normal Hearing ◽  
Speech Stimuli ◽  
Novel Method ◽  
Cortical Auditory Evoked Potentials

Introduction: Cortical auditory evoked potentials can provide objective information about the highest level of the auditory system. Aim: The purpose of the authors was to introduce a new tool, the “HEARLab” which can be routinely used in clinical practice for the measurement of the cortical auditory evoked potentials. In addition, they wanted to establish standards of the analyzed parameters in subjects with normal hearing. Method: 25 adults with normal hearing were tested with speech stimuli, and frequency specific examinations were performed utilizing pure tone stimuli. Results: The findings regarding the latency and amplitude analyses of the evoked potentials confirm previously published results of this novel method. Conclusions: The HEARLAb can be a great help when performance of the conventional audiological examinations is complicated. The examination can be performed in uncooperative subjects even in the presence of hearing aids. The test is frequency specific and does not require anesthesia. Orv. Hetil., 2014, 155(38), 1524–1529.

scholarly journals Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Jesus Simal-Gandara ◽  
Dalia M. Kopustinskiene ◽  
...  
Keyword(s):  
Blood Cells ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Experimental Studies ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Current Review ◽  
Mesh Terms ◽  
Online Databases ◽  
Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

scholarly journals Molecular mechanisms of Zika virus teratogenesis from animal studies: a systematic review protocol

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gabriela Elis Wachholz ◽  
Julia do Amaral Gomes ◽  
Juliano André Boquett ◽  
Fernanda Sales Luiz Vianna ◽  
Lavínia Schuler-Faccini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Zika Virus ◽  
Methodological Quality ◽  
Molecular Mechanisms ◽  
Grey Literature ◽  
Standard Form ◽  
Teratogenic Effect ◽  
Control Group

Abstract Background Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability. Systematic review registration PROSPERO CRD42019157316

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