Abstract
OBJECTIVE
The degeneration of hair cells and spiral ganglion neurons (SGNs) is an important pathologic process in the development of sensorineural hearing loss. In a murine model, predictable and reproducible damage to SGNs occurs through the application of ouabain to the round window. Recent evidence has shown that the chemokine stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant of hematopoietic stem cells (HSCs) and provides trophic support to injured tissues during development and maturation. Our hypothesis for the current study is that engrafted HSCs and expression of SDF-1 play an important role in protecting SGNs and preventing further degeneration in the setting of cochlear injury. 1) Understand the role of chemoattractants in the mouse inner ear after injury. 2) Determine the applicability of hematopoietic stem cell transplantation as therapy for sensorineural hearing loss in the mouse model.
METHOD
Bone marrow (BM) cells obtained from transgenic mice expressing enhanced green fluorescent protein (GFP) were injected into tail veins of adult irradiated recipient mice for HSC transplantation. HSC engraftment patterns in the transplanted mice were analyzed three and seven days after ouabain application. Auditory brainstem response (ABR) and the expression of SDF-1 mRNA and protein were examined one, 3, 7, 14, and 30 days after application of ouabain in adult mice without HSC transplantation.
RESULTS
Following ouabain application, HSC engraftment was significantly increased in the auditory nerve compared to control ears in BM-transplanted mice. Real-time RT-PCR for SDF demonstrates increased mRNA expression following ouabain injury in non-transplanted mice. A significant increase in SDF protein expression was also observed using immunolabeling techniques.
CONCLUSION
SDF-1 expression and HSC engraftment is increased in the auditory nerve following cochlear injury. Further knowledge about the cochlear microenvironment, including SDF-1, is critical to maximizing HSC engraftment in the injured cochlea and providing a therapeutic option for sensorineural hearing loss.