The potential of bone marrow derived mesenchymal stem cells in treating cisplatin induced sensorineural hearing loss in a guinea pig animal model

Tissue Cell. 2024 Dec 30:93:102703. doi: 10.1016/j.tice.2024.102703. Online ahead of print.

Abstract

Background: Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Current solutions for SNHL, including hearing aids, cochlear implants, and hearing assistive devices, do not provide consistent results and fail to address the underlying pathology of hair cell and ganglion cell damage. Stem cell therapy is a cornerstone in regenerative medicine. It provides new hope to treat SNHL by replacing/regenerating damaged hair cells and ganglion cells. Mesenchymal stem cells are an interesting choice in stem cell therapy.

Aim of the work: Evaluation of bone marrow derived mesenchymal stem cell (BM-MSC) transplantation to improve SNHL management.

Methods: An experimental study was conducted using 40 recipient guinea pigs, randomly divided into four groups, along with 4 donor guinea pigs for bone marrow harvesting to isolate BM-MSC. Group I (12 animals) served as the control, receiving neither ototoxic drugs nor stem cell treatment. Group II (12 animals) received intraperitoneal cisplatin (1.5 mg/kg/day for 8 days) to induce sensorineural hearing loss, but no stem cell treatment. Group III (12 animals) received IP cisplatin to induce SNHL, followed by BM-MSC transplantation via round window injection one week later. Groups I, II, and III were euthanized 5 weeks after the last cisplatin injection, and their cochleae were examined using light microscopy, scanning electron microscopy, and fluorescent light microscopy to assess the effect of stem cell transplantation on the recovery of neurosensory tissue in the cochlea after cisplatin treatment. Group IV (4 animals) received IP cisplatin to induce SNHL, followed by transplantation of fluorescein-labeled BM-MSC (FLBM-MSC) via round window injection one week later and were euthanized after one week to study stem cell migration and homing.

Results: Light Microscopy: Group I exhibited a normal structure in the organ of Corti, spiral ganglion, and stria vascularis. In contrast, Group II demonstrated degeneration in these areas. Group III showed a preserved structure in the organ of Corti, spiral ganglion, and stria vascularis, with statistically significant differences compared to Group II (p < .05). Scanning Electron Microscopy: Group I displayed normal ultrastructure of the organ of Corti, while Group II showed a loss of outer hair cells. Group III demonstrated preserved ultrastructure of the organ of Corti. Fluorescent Light Microscopy: In Group IV, transplanted cells were observed to home into the cochlear lateral wall, organ of Corti, and spiral ganglion.

Conclusion: The study showed that BM-MSCs, delivered via round window injection, can migrate to cochlear regions and protect key structures after cisplatin-induced SNHL in guinea pigs, suggesting their potential as a treatment for SNHL.

Keywords: Bone marrow derived mesenchymal stem cells; Cisplatin; Hearing loss; Mesenchymal stem cells; Sensorineural hearing loss; Stem cell therapy.