Abstract

Objectives As a homing factor of stem cell, stromal derived factor-1 (SDF-1) is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg) dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg). The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

Highlights

  • Stromal derived factor-1 (SDF-1) is a cytokine for stimulating the homing of stem cells into injured organs

  • auditory brainstem response (ABR) evaluations were performed at 0, 3, 5, 7, 10, and 14 days after drug administration to test whether the combined effect of kanamycin/furosemide is able to induce hearing loss in mice

  • We compared the average ABR thresholds for the four groups, which was measured with click sounds (Figure 2(a))

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Summary

Introduction

Stromal derived factor-1 (SDF-1) is a cytokine for stimulating the homing of stem cells into injured organs. The expression of SDF-1 in injured tissue correlates with recruitment of stem cells and tissue regeneration. Recent studies have shown that homing of mesenchymal stem cells (MSCs) across the blood-brain barrier (BBB) occurred in ischemic brain tissue. Myocardial protection by homing of stem cells was shown in myocardial infarction via mobilization of the stem cells into the injured myocardial tissue and increase in local angiogenesis after myocardial infarction. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. Several studies showed that mice can be used as models for aminoglycoside-induced hearing loss using a “one-shot” protocol, in which a single dose of kanamycin is accompanied by a dose of the loop diuretic furosemide [1, 2]

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