Mesenchymal stem cells for sensorineural hearing loss: protocol for a systematic review of preclinical studies

Abstract Background Sensorineural hearing loss (SNHL) is the most common form of hearing impairment and is characterized by a loss of receptor hair cells and/or spiral ganglion neurons. Regenerative stem cell therapy could potentially restore normal hearing and slow the progression of hearing loss in patients. Preclinical animal studies have demonstrated that mesenchymal stem cells (MSCs) could be a promising new therapy for this condition. These findings have prompted investigators to begin human clinical trials to assess the safety and efficacy of MSCs for the treatment of SNHL. The objective of the proposed systematic review is to examine the efficacy of MSCs as a therapy for SNHL in animal models. Methods We will include preclinical animal studies of SNHL in which MSCs are administered, and outcomes are compared against MSC-naïve controls. The primary outcome will include audiologic tests that are routinely used in experimental studies of hearing loss, such as auditory brainstem response (ABR) and distortion product otoacoustic emissions testing (DPOAE). Secondary outcomes will include histology, microscopy, gene protein expression, and behavioral responses of animals. Electronic searches of MEDLINE via PubMed, Scopus, ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be performed. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias and publication bias will be assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool and Funnel Plots/Egger’s regression tests, respectively. Discussion This systematic review will provide a summary of the efficacy of MSC therapy in animal models of SNHL, utilizing functional hearing assessment as a primary outcome. Findings from this review are important because they can elucidate research gaps that should be addressed in future preclinical studies and in turn can be translated into clinical studies. Systematic review registration CAMARADES ( http://www.dcn.ed.ac.uk/camarades/ )