Integrating Regenerative Medicine and Stem Cell Therapy in Hearing Restoration: A Systematic Review

Abstract

Hearing loss can adversely affect communication and language development and is associated with cognitive decline.Current treatments, including hearing aids and cochlear implants, can improve auditory function but do not regenerate damaged sensory cells.Stem-cell-based approaches have therefore attracted increasing interest as potential regenerative strategies, and stem cells have been used to generate inner-ear progenitor and hair-cell-like cells in vitro for hearing-loss research.This systematic review aimed to evaluate the efficacy, safety, and regenerative potential of stem-cell-based therapies and related regenerative approaches relevant to hearing restoration.The included evidence spanned distinct levels of investigation: in vitro studies primarily informed regenerative and differentiation potential, animal studies evaluated selected auditory, cellular, and histological outcomes, and two small human studies provided preliminary clinical observations.Related genetic strategies were also included where directly relevant to auditory regeneration.A literature search of PubMed and Google Scholar was conducted to identify relevant studies published between 2010 and 2025.Eligible studies investigated stem-cell-based therapies, stem/progenitor-cell approaches, or closely related regenerative strategies relevant to hearing restoration in human participants, animal models, or in vitro experimental systems.Approaches included mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), related progenitor-cell strategies, and regenerative genetic approaches directly relevant to auditory restoration.Studies were required to report measurable auditory, cellular, histological, or functional outcomes relevant to inner-ear regeneration or hearing-related function.Seventeen studies met the inclusion criteria.In vitro studies demonstrated differentiation of stem or progenitor cells toward inner-ear sensory and neural phenotypes, supporting regenerative potential but not clinical efficacy.Animal studies reported variable findings, including improvements or preservation in selected auditory measures such as auditory brainstem response (ABR) thresholds, alongside cellular and histological changes in some models; other studies demonstrated no significant functional improvement.The two small human studies reported no major treatment-related adverse events during their limited follow-up, while auditory outcomes were inconsistent.Substantial heterogeneity in cell sources, delivery methods, experimental models, and outcome measures limited direct comparison between studies.Laboratory and animal studies support further investigation of stem-cell-based and related regenerative approaches for sensorineural hearing loss.However, clinical efficacy has not been established, and the available human evidence is limited to preliminary short-term observations from small studies.Standardized protocols and larger, long-term human studies are required to establish safety, durability, and clinical effectiveness.