Brainstem Response Changes of Noise-Induced Auditory Damage after Stem Cell Injection: Systematic Review of Animal Studies and Meta-Analysis Hearing loss and cell therapy
Iranian Journal of Child Neurology,
Vol. 20 No. 3 (2026),
1 June 2026
,
Page 13-23
https://doi.org/10.22037/ijcn.v20i3.47686
Abstract
Objectives:
As permanent hearing loss is irreversible, individuals often rely on hearing aids or cochlear implants as effective rehabilitation solutions. Stem cell therapy has been used this disability at the level of preclinical studies and effectiveness has not been determined to improve of auditory brainstem response (ABR) and restore damaged hair cells of cochlea. This systematic review shows the role of stem cell injection on ABR threshold changes in noise induced hearing loss (NIHL) models.
Materials & Methods:
Search strategies for Embase, PubMed, and Web of Science were performed based on keywords stem cell, hearing loss, and noise from 2000 to 2024. Nine studies were evaluated for study variables and risk of bias, and only six studies were analyzed to estimate effect size of auditory threshold.
Results:
The broadband noise was the most common noise to create NIHL model. The improvement of ABR threshold was estimated -2.46, 95% (CI: -3.26, -1.66) after stem cell injection. Significant mean differences were observed in ABR-threshold for local injection (n = 148) and mesenchymal stem cell (MSC) injection (n = 129) with high heterogeneity between studies.
Conclusion:
According to high heterogeneity between studies, it may be concluded that MSC, systemic injection, and human-derived cells are effective in recovery of auditory brainstem function.
- auditory brain stem response
- Stem cell
- Noise induced hearing loss
How to Cite
References
Ahmed MM, Allard RJ, Esquivel CR. Noise-induced hearing loss treatment: systematic review and meta-analysis. Military Medicine. 2022;187(5-6):e661-e6.
Waqas M, Gao S, Ali MK, Ma Y, Li W. Inner ear hair cell protection in mammals against the noise-induced cochlear damage. Neural Plasticity. 2018.
Le TN, Straatman LV, Lea J, Westerberg B. Current insights in noise-induced hearing loss: a literature review of the underlying mechanism, pathophysiology, asymmetry, and management options. Journal of Otolaryngology-Head & Neck Surgery. 2017;46(1):1-15.
Nacher-Soler G, Garrido JM, Rodríguez-Serrano F. Hearing regeneration and regenerative medicine: present and future approaches. Archives of Medical Science. 2019;15(4):957-67.
Oroei M, Ahadi M. Stem Cell Therapy in Children With Sensorineural Hearing Loss: A Narrative Review. Journal of Pediatrics Review. 2021;9(3):219-28.
Chen J, Hong F, Zhang C, Li L, Wang C, Shi H, et al. Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea. Stem Cell Research & Therapy. 2018;9(1):230.
Simoni E, Orsini G, Chicca M, Bettini S, Franceschini V, Martini A, et al. Regenerative medicine in hearing recovery. Cytotherapy. 2017;19(8):909-15.
Parker MA, Corliss DA, Gray B, Anderson JK, Bobbin RP, Snyder EY, et al. Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hearing Research. 2007;232(1-2):29-43.
Revoltella RP, Papini S, Rosellini A, Michelini M, Franceschini V, Ciorba A, et al. Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise. Cell Transplant. 2008;17(6):665-78.
Fetoni AR, Lattanzi W, Eramo SLM, Barba M, Paciello F, Moriconi C, et al. Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma. Frontiers in cellular neuroscience. 2014;8:334.
Xu Y-p, Shan X-d, Liu Y-y, Pu Y, Wang C-y, Tao Q-l, et al. Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats. Neuroscience Letters. 2016;616:19-25.
Xu LW, Yuan SL, Chen W, Ma YY, Luo Y, Guo WW, et al. Transplantation and Tracking of the Human Umbilical Cord Mesenchymal Stem Cell Labeled with Superparamagnetic Iron Oxide in Deaf Pigs. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology. 2020;303(3):494-505.
Chorath K, Willis M, Morton-Gonzaba N, Moreira A. Mesenchymal stem cells for sensorineural hearing loss: a systematic review of preclinical studies. Molecular biology reports. 2020;47(6):4723-36.
Pourbakht A, Yamasoba T. Cochlear damage caused by continuous and intermittent noise exposure. Hearing Research. 2003;178(1):70-8.
Hooijmans CR, Rovers MM, De Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC medical research methodology. 2014;14:1-9.
Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I² index? Psychological methods. 2006;11(2):193.
Sullivan JM, Cohen MA, Pandit SR, Sahota RS, Borecki AA, Oleskevich S. Effect of epithelial stem cell transplantation on noise-induced hearing loss in adult mice. Neurobiol Dis. 2011;41(2):552-9.
Choi BY, Song J-J, Chang SO, Kim SU, Oh SH. Intravenous administration of human mesenchymal stem cells after noise-or drug-induced hearing loss in rats. Acta oto-laryngologica. 2012;132(sup1):S94-S102.
Ajalloueyan M, Kouhi A, Asgari A, Salem M, Hasanalifard M. Stem cell transplantation in noise induced hearing loss. International Journal of Pediatric Otorhinolaryngology. 2013;77(4):469-72.
Warnecke A, Harre J, Shew M, Mellott AJ, Majewski I, Durisin M, et al. Successful Treatment of Noise-Induced Hearing Loss by Mesenchymal Stromal Cells: An RNAseq Analysis of Protective/Repair Pathways. Front Cell Neurosci. 2021;15:656930.
Lee DS, Pan YL, Hsu YC. Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage. J Vis Exp. 2023(192).
Cody A, Robertson D. Variability of noise-induced damage in the guinea pig cochlea: electrophysiological and morphological correlates after strictly controlled exposures. Hearing research. 1983;9(1):55-70.
McFadden SL, Woo JM, Michalak N, Ding D. Dietary vitamin C supplementation reduces noise-induced hearing loss in guinea pigs. Hearing research. 2005;202(1-2):200-8.
Mohammadkhani G, Pourbakht A, Khanavi M, Faghihzadeh S. Protective effect of silymarin on noise-induced hearing loss in Guinea pigs. Iranian Red Crescent Medical Journal. 2013;15(11).
Akil O, Oursler A, Fan K, Lustig LR. Mouse auditory brainstem response testing. Bio-protocol. 2016;6(6):e1768-e.
Ullah M, Liu DD, Thakor AS. Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. iScience. 2019;15:421-38.
Peyvandi AA, Roozbahany NA, Peyvandi H, Abbaszadeh HA, Majdinasab N, Faridan M, et al. Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma. Neural Regen Res. 2018;13(1):154-60.
Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28(7):299-307.
Bianchi ME, Mezzapelle R. The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration. Frontiers in Immunology. 2020;11.
Zhang W, Sun JZ, Han Y, Chen J, Liu H, Wang Y, et al. CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice. Mol Med Rep. 2016;13(5):4357-64.
Baumgartner LS, Moore E, Shook D, Messina S, Day MC, Green J, et al. Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children. J Audiol Otol. 2018;22(4):209-22.
- Abstract Viewed: 2 times