scholarly journals Stem Cell-Based Therapeutic Approaches to Restore Sensorineural Hearing Loss in Mammals

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Muhammad Waqas ◽  
Iram Us-Salam ◽  
Zainab Bibi ◽  
Yunfeng Wang ◽  
He Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hearing Loss ◽  
Stem Cell ◽  
Sensorineural Hearing Loss ◽  
Hearing Aids ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Sensorineural Hearing ◽  
Sensory Structures ◽  
Ganglion Neurons

The hair cells that reside in the cochlear sensory epithelium are the fundamental sensory structures responsible for understanding the mechanical sound waves evoked in the environment. The intense damage to these sensory structures may result in permanent hearing loss. The present strategies to rehabilitate the hearing function include either hearing aids or cochlear implants that may recover the hearing capability of deaf patients to a limited extent. Therefore, much attention has been paid on developing regenerative therapies to regenerate/replace the lost hair cells to treat the damaged cochlear sensory epithelium. The stem cell therapy is a promising approach to develop the functional hair cells and neuronal cells from endogenous and exogenous stem cell pool to recover hearing loss. In this review, we specifically discuss the potential of different kinds of stem cells that hold the potential to restore sensorineural hearing loss in mammals and comprehensively explain the current therapeutic applications of stem cells in both the human and mouse inner ear to regenerate/replace the lost hair cells and spiral ganglion neurons.

scholarly journals Autophagy Regulates the Survival of Hair Cells and Spiral Ganglion Neurons in Cases of Noise, Ototoxic Drug, and Age-Induced Sensorineural Hearing Loss

2021 ◽  
Vol 15 ◽  
Author(s):  
Lingna Guo ◽  
Wei Cao ◽  
Yuguang Niu ◽  
Shuangba He ◽  
Renjie Chai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Spiral Ganglion ◽  
Sensorineural Hearing ◽  
Spiral Ganglion Neurons ◽  
Core Components ◽  
Spontaneous Regeneration ◽  
Ganglion Neurons

Inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) are the core components of the auditory system. However, they are vulnerable to genetic defects, noise exposure, ototoxic drugs and aging, and loss or damage of HCs and SGNs results in permanent hearing loss due to their limited capacity for spontaneous regeneration in mammals. Many efforts have been made to combat hearing loss including cochlear implants, HC regeneration, gene therapy, and antioxidant drugs. Here we review the role of autophagy in sensorineural hearing loss and the potential targets related to autophagy for the treatment of hearing loss.

Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms

2020 ◽  
pp. jmedgenet-2020-106892
Author(s):  
Xue Gao ◽  
Sha-Sha Huang ◽  
Shi-Wei Qiu ◽  
Yu Su ◽  
Wei-Qian Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Noonan Syndrome ◽  
Sensorineural Hearing ◽  
Supporting Cells ◽  
Pathogenic Variants ◽  
Underlying Mechanisms ◽  
Ganglion Neurons ◽  
Multiple Lentigines

BackgroundGermline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which share common skin and facial symptoms, cardiac anomalies and retardation of growth. Hearing loss is considered an infrequent feature in patients with NSML/NS. However, in our cohort, we identified a group of patients with PTPN11 pathogenic variants that were primarily manifested in congenital sensorineural hearing loss (SNHL). This study evaluated the incidence of PTPN11-related NSML or NS in patients with congenital SNHL and explored the expression of PTPN11 and the underlying mechanisms in the auditory system.MethodsA total of 1502 patients with congenital SNHL were enrolled. Detailed phenotype-genotype correlations were analysed in patients with PTPN11 variants. Immunolabelling of Ptpn11 was performed in P35 mice. Zebrafish with Ptpn11 knockdown/mutant overexpression were constructed to further explore mechanism underlying the phenotypes.ResultsTen NSML/NS probands were diagnosed via the identification of pathogenic variants of PTPN11, which accounted for ~0.67% of the congenital SNHL cases. In mice cochlea, Shp2, which is encoded by Ptpn11, is distributed in the spiral ganglion neurons, hair cells and supporting cells of the inner ear. In zebrafish, knockdown of ptpn11a and overexpression of mutant PTPN11 were associated with a significant decrease in hair cells and supporting cells. We concluded that congenital SNHL could be a major symptom in PTPN11-associated NSML or NS. Other features may be mild, especially in children.ConclusionScreening for PTPN11 in patients with congenital hearing loss and variant-based diagnoses are recommended.

scholarly journals Research Progress on Flat Epithelium of the Inner Ear

2020 ◽  
pp. 775-785
Author(s):  
L HE ◽  
J-Y GUO ◽  
K LIU ◽  
G-P WANG ◽  
S-S GONG
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Noise Exposure ◽  
Sensory Epithelium ◽  
Sensorineural Hearing ◽  
Research Progress ◽  
Supporting Cells ◽  
Mesenchymal Transition

Sensorineural hearing loss and vertigo, resulting from lesions in the sensory epithelium of the inner ear, have a high incidence worldwide. The sensory epithelium of the inner ear may exhibit extreme degeneration and is transformed to flat epithelium (FE) in humans and mice with profound sensorineural hearing loss and/or vertigo. Various factors, including ototoxic drugs, noise exposure, aging, and genetic defects, can induce FE. Both hair cells and supporting cells are severely damaged in FE, and the normal cytoarchitecture of the sensory epithelium is replaced by a monolayer of very thin, flat cells of irregular contour. The pathophysiologic mechanism of FE is unclear but involves robust cell division. The cellular origin of flat cells in FE is heterogeneous; they may be transformed from supporting cells that have lost some features of supporting cells (dedifferentiation) or may have migrated from the flanking region. The epithelial-mesenchymal transition may play an important role in this process. The treatment of FE is challenging given the severe degeneration and loss of both hair cells and supporting cells. Cochlear implant or vestibular prosthesis implantation, gene therapy, and stem cell therapy show promise for the treatment of FE, although many challenges remain to be overcome.

scholarly journals Therapeutic Efficacy of Bone Marrow Derived Mesenchymal Stem Cells in Ototoxic Sensorineural Hearing Loss

2020 ◽  
Vol 63 (12) ◽  
pp. 564-569
Author(s):  
Subin Kim ◽  
Yoon Hee Kwon ◽  
In Beom Kim ◽  
Young Jun Seo ◽  
Jae Sang Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hearing Loss ◽  
Stem Cell ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Control Group ◽  
Clinical Grade ◽  
Brainstem Response

Background and Objectives Ototoxic sensorineural hearing loss causes permanent hearing loss in most cases. Recently there have been many reports describing cell base therapy with stem cells that has some effect on hearing recovery. We evaluated the efficacy of clinical grade, pre-made, human bone marrow derived mesenchymal stem cells (BM-MSCs) in ototoxic deaf animal model.Materials and Method BM-MSCs were cultured in a clinical grade laboratory. The animals were divided into 2 groups as follows: a saline injected control group and a stem cell injected group (MSC-group). Cultured MSCs were transplanted into the brachial vein of the deaf mice model. We recorded auditory brainstem response (ABR) and conducted immunohistochemistry at 1, 3, and 5 weeks.Results After the transplantation of MSC, a significant improvement in the hearing threshold of ABR was observed in the MSC transplanted group. Five weeks after transplantation of MSCs, hair cell regeneration was confirmed from the basal to the apex of the cochlea in fluorescent dyed image under the microscope compared to the control group.Conclusion BM-MSCs were effective in an acute ototoxic deaf animal model. These results show that stem cell transplantation mediate inner ear regeneration.

Role of Stem Cells in Treatment of Sensorineural Hearing Loss

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hesham El-Halaby ◽  
Ayman El-Kahky ◽  
Hesham Taha ◽  
Fatma Abu-Zahra ◽  
Ihab Nada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Guinea Pigs ◽  
Sensorineural Hearing ◽  
Group A ◽  
Group B

Abstract Background More than 5% of the world population lives with a hearing impairment. The main factors responsible for hearing degeneration are ototoxic drugs, aging, continued exposure to excessive noise and infections. The pool of adult stem cells in the inner ear drops dramatically after birth, and therefore an endogenous cellular source for regeneration is absent. Objectives The purpose of this study is to evaluate the role of mesenchymal stem cells in the treatment of severe to profound sensorineural hearing loss as regarding permanent regeneration of the auditory hair cells. Materials and Methods It is a prospective study which was performed in the period of May 2019 till December 2019 and encountered 40 adult male guinea pigs, aged 6 to 8 weeks (body weight 250-500 gram). 30 guinea pigs had been subjected to right side intratympanic injection of Garamycin sulphate to induce sensorineural hearing loss then the 30 animals were subdivided after that into 2 groups; Group A (15 animals) were treated by mesenchymal stem cells implantation in right inner ear cochlea and group B (15 animals) left untreated and the remaining 10 guinea pigs; Group C left normally as a control group. Results As respect to histopathological examination, 100% of animals in group B (n = 15) expressed severe degenerative changes in the peripheral organs. The outer hair cells showed severe destruction with individual loss of the inner hair cells. Also the supporting cells of Corti’s organ presented severe necrosis which was more relevant in the basal turns. We used the bone marrow differentiated MSCs to evaluate their potency in regeneration of the damaged and lost sensorineural elements in gentamicin injured cochlea. In group A (n = 15) 9 out of 15 (60%) expressed profound regeneration and 4 out of 15 (26.66%) expressed early regenerative changes, while 2 animals (13.33%) expressed less degenerative changes which impacted by gentamicin. Conclusion Stem cell transplantation is a promising approach for hearing loss therapy. The choice of stem cell type for transplantation plays a crucial role in the outcome. MSCs are multipotent cells that can be isolated from adult bone marrow and can be induced to differentiate into a variety of tissues in vitro and in vivo.

Otologics Fully Implantable Hearing Device Phase II Results

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P57-P57
Author(s):  
Drew M Horlbeck ◽  
Herman A Jenkins ◽  
Ben J Balough ◽  
Michael E Hoffer
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Phase Ii ◽  
Hearing Aids ◽  
Repeated Measures ◽  
Pure Tone ◽  
Sound Field ◽  
Sensorineural Hearing ◽  
Significant Difference ◽  
Hearing Device

Objective The efficacy of the Otologics Fully Implantable Hearing Device (MET) was assessed in adult patients with bilateral moderate to severe sensorineural hearing loss. Methods Surgical insertion of this totally implanted system was identical to the Phase I study. A repeated-measures within-subjects design assessed aided sound field thresholds and speech performances with the subject's own, appropriately fit, walk-in hearing aid(s) and the Otologics Fully Implantable Hearing Device. Results Six- and 12-month Phase II data will be presented. Ten patients were implanted and activated as part Phase II clinical trial. Three patients were lost to long term follow-up due to two coil failures and one ossicular abnormality preventing proper device placement. No significant differences between preoperative (AC = 59 dB, BC = 55 dB) and postoperative (AC = 61 dB, BC = 54 dB) unaided pure tone averages were noted (p < 0.05). Pure tone average implant aided thresholds (41 dB) were equivalent to that of walk-in-aided (37 dB) condition with no significant difference (p < 0.05) between patients’ walk-in-aided individual frequency thresholds and implant-aided thresholds. Word recognition scores and hearing in noise scores were similar between the walk-in-aided and for the implant-aided condition. Patient benefit scales will be presented at all end points. Conclusions Results of the Otologics MET Fully Implantable Hearing Device Phase II trial provide evidence that this fully implantable device is a viable alternative to currently available hearing aids in patients with sensorineural hearing loss.

scholarly journals Noise-induced and age-related hearing loss:  new perspectives and potential therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 927 ◽  
Author(s):  
M Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Cell Loss ◽  
Sensorineural Hearing ◽  
Hair Cell Loss ◽  
Age Related ◽  
Age Related Hearing Loss

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

scholarly journals Investigating the Impact of Hearing Aid Use and Auditory Training on Cognition, Depressive Symptoms, and Social Interaction in Adults With Hearing Loss: Protocol for a Crossover Trial (Preprint)

2017 ◽  
Author(s):  
Joanna Nkyekyer ◽  
Denny Meyer ◽  
Peter J Blamey ◽  
Andrew Pipingas ◽  
Sunil Bhar
Keyword(s):  
Hearing Loss ◽  
Depressive Symptoms ◽  
Social Interaction ◽  
Sensorineural Hearing Loss ◽  
Hearing Aids ◽  
Hearing Aid ◽  
Sensorineural Hearing ◽  
Auditory Training ◽  
Face To Face ◽  
Hearing Aid Use

BACKGROUND Sensorineural hearing loss is the most common sensory deficit among older adults. Some of the psychosocial consequences of this condition include difficulty in understanding speech, depression, and social isolation. Studies have shown that older adults with hearing loss show some age-related cognitive decline. Hearing aids have been proven as successful interventions to alleviate sensorineural hearing loss. In addition to hearing aid use, the positive effects of auditory training—formal listening activities designed to optimize speech perception—are now being documented among adults with hearing loss who use hearing aids, especially new hearing aid users. Auditory training has also been shown to produce prolonged cognitive performance improvements. However, there is still little evidence to support the benefits of simultaneous hearing aid use and individualized face-to-face auditory training on cognitive performance in adults with hearing loss. OBJECTIVE This study will investigate whether using hearing aids for the first time will improve the impact of individualized face-to-face auditory training on cognition, depression, and social interaction for adults with sensorineural hearing loss. The rationale for this study is based on the hypothesis that, in adults with sensorineural hearing loss, using hearing aids for the first time in combination with individualized face-to-face auditory training will be more effective for improving cognition, depressive symptoms, and social interaction rather than auditory training on its own. METHODS This is a crossover trial targeting 40 men and women between 50 and 90 years of age with either mild or moderate symmetric sensorineural hearing loss. Consented, willing participants will be recruited from either an independent living accommodation or via a community database to undergo a 6-month intensive face-to-face auditory training program (active control). Participants will be assigned in random order to receive hearing aid (intervention) for either the first 3 or last 3 months of the 6-month auditory training program. Each participant will be tested at baseline, 3, and 6 months using a neuropsychological battery of computer-based cognitive assessments, together with a depression symptom instrument and a social interaction measure. The primary outcome will be cognitive performance with regard to spatial working memory. Secondary outcome measures include other cognition performance measures, depressive symptoms, social interaction, and hearing satisfaction. RESULTS Data analysis is currently under way and the first results are expected to be submitted for publication in June 2018. CONCLUSIONS Results from the study will inform strategies for aural rehabilitation, hearing aid delivery, and future hearing loss intervention trials. CLINICALTRIAL ClinicalTrials.gov NCT03112850; https://clinicaltrials.gov/ct2/show/NCT03112850 (Archived by WebCite at http://www.webcitation.org/6xz12fD0B).

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