Role of Stem Cells in Treatment of Sensorineural Hearing Loss

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.

Download Full-text

Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

BioMed Research International ◽

10.1155/2014/856019 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Chang-qiang Tan ◽

Xia Gao ◽

Lang Guo ◽

He Huang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Inner Ear ◽

Sensorineural Hearing ◽

Scala Tympani ◽

Auditory Brain Stem Response ◽

Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groupsP<0.05. Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

Download Full-text

The role of intratympanic dexamethasone in sudden sensorineural hearing loss

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20201551 ◽

2020 ◽

Vol 6 (5) ◽

pp. 821

Author(s):

Vivek Samor ◽

Sukhdev Khadav ◽

Pooja Arya ◽

Deepchand . ◽

Ramniwas Dhaka

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Interaural Time Difference ◽

Determine Factor ◽

Sudden Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Oral Steroids ◽

Group A ◽

Group B ◽

Intratympanic Dexamethasone

Background: Present study was conducted to assess the efficacy of intratympanic dexamethasone in patients with sudden sensorineural hearing loss and to determine factor affecting treatment outcome for sudden sensorineural hearing loss.Methods: Prospective study was conducted on 24 patients of sudden sensorineural hearing loss between October 2019 to February 2020 in the department of ENT, OPD, SPMC, Bikaner. Group A were given oral steroids: prednisolone 1 mg/kg/day (maximal dose is 60 mg/day) full dose 14 days, then tapered over next 14 days. Group B were given intratympanic dexamethasone 4 mg/ml, 0.5 ml into middle ear space (into the posterior inferior quadrant) every 7 days for a total of 4 weeks. Audiogram was performed at end of every week for 4 weeks. Results: Overall, 58% (n=14) patients showed improvement in pure-tone average. For ≤3 days of presentation; out of total 6 patients, 83.33% cases recovered. For 4 to 7 days of presentation; out of total 10 patients, 80% cases recovered. For 8 to 14 days presentation; out of total 8 patients 12.5% cases recovered (p=0.005).Conclusions: We suggest the treatment approach in which interaural time difference is used adjuvantly with oral steroids.

Download Full-text

Sudden Sensorineural Hearing Loss: Comparative Study of Different Treatment Modalities

International Archives of Otorhinolaryngology ◽

10.1055/s-0037-1605376 ◽

2017 ◽

Vol 22 (03) ◽

pp. 245-249 ◽

Cited By ~ 4

Author(s):

Ahmed Khater ◽

Mohammad El-Anwar ◽

Ahmad Nofal ◽

Atef Elbahrawy

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Antiviral Therapy ◽

Sudden Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Treatment Modalities ◽

Early Administration ◽

Vasoactive Substances ◽

Group A ◽

Group B

Introduction Idiopathic sudden sensorineural hearing loss (ISSNHL) is hearing loss of at least 30 dB in at least 3 contiguous frequencies within at least 72 hours. There are many different theories to explain it, and many different modalities are used for its management, such as: systemic steroids (SSs), intratympanic steroid injection (ITSI), hyperbaric oxygen therapy (HOT), antiviral drugs, and vasodilators or vasoactive substances. Objectives This study aims to evaluate the efficacy of the combination of the most common treatment modalities of ISSNHL and to compare the results if HOT was not one of the treatment modalities administered. Methods The study was conducted with 22 ISSNHL patients with ages ranging from 34 to 58 years. The patients were divided into 2 groups; group A included 11 patients managed by SSs, ITSI, antiviral therapy, and HOT simultaneously, and group B included 11 patients exposed to the aforementioned modalities, with the exception of HOT. Results After one month, all of the patients in group A showed total improvement in hearing in all frequencies, with pure tone average (PTA) of 18.1 ± 2.2, while in group B, 5/11 (45.5%) patients showed total improvement, and 6 /11 (54.5%) patients showed partial improvement, with a total mean PTA of 28.1 ± 8.7. Conclusion The early administration of HOT in combination with other clinically approved modalities (SSs, ITSI, antiviral therapy) provides better results than the administration of the same modalities, with the exception of HOT, in the treatment of ISSNHL.

Download Full-text

Retracted: Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model

BioMed Research International ◽

10.1155/2017/9539385 ◽

2017 ◽

Vol 2017 ◽

pp. 1-1 ◽

Cited By ~ 1

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Hearing Loss ◽

Guinea Pig ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Pig Model ◽

Marrow Mesenchymal Stem Cells ◽

Guinea Pig Model

Download Full-text

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

Neural Plasticity ◽

10.1155/2020/8829660 ◽

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.

Download Full-text

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

Korean Journal of Otorhinolaryngology - Head and Neck Surgery ◽

10.3342/kjorl-hns.2020.00759 ◽

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.

Download Full-text

Long non-coding RNA-2271 promotes osteogenic differentiation in human bone marrow stem cells

Open Life Sciences ◽

10.1515/biol-2018-0049 ◽

2018 ◽

Vol 13 (1) ◽

pp. 404-412 ◽

Cited By ~ 1

Author(s):

Li-Cheng Xi ◽

Hong-Yu Li ◽

Dong Yin

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Osteogenic Differentiation ◽

Control Group ◽

Alizarin Red ◽

Alp Activity ◽

Human Bmscs ◽

Group A ◽

Group B

AbstractBackgroundHuman bone marrow mesenchymal stem cells (BMSCs) are of great significance for bone regeneration and bone formation. Long non-coding RNAs (lncRNAs) may be involved in modulating cell differentiation. This study aimed to investigate the role of lncR-2271 in promoting osteogenic differentiation in human BMSCs.MethodsHuman BMSCs were infected using lncR-2271 overexpression (group A) with lentiviral system or transfected with lncR-2271 siRNA (group B). Cells transfected with scrambled plasmids were used as a negative control (group C). Osteogenesis markers were evaluated using alkaline phosphatase (ALP) activity, RUNX2 and osterix (OSX) at protein levels and calcification by Alizarin Red staining.ResultsBMSCs from group A showed significantly higher ALP activity compared to BMSCs in group B and control group (group C) at both days 7 and 14 following osteogenic induction; ALP activity was significantly lower in the group B compared to the group C. RUNX2 and OSX protein expressions were significantly higher in group A and significantly lower in group B, compared to those in group C, respectively. At day 21, calcification in human BMSCs in group A was significantly higher compared to groups B and C as shown by Alizarin Red staining; calcification was significantly lower in group B compared to group C.ConclusionOur data suggested lncR-2271 played a role in promoting osteogenic differentiation in human BMSCs. This study is the first to illustrate the important role of lncR-2271 in bone formation.

Download Full-text