A Simple Model for Inducing Optimal Increase of with Aminoglycoside Ototoxicity.

OBJECTIVES

As a homing factor of stem cell, stromal derived factor-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 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 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 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. 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 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.