Stem Cell Transplantation in Mice with Genetic Deafness and Optimization of the Transplantation Condition
Date Issued
2011
Date
2011
Author(s)
Lin, Yi-Tsen
Abstract
Part I: Stem Cell Transplantation in SLC26A4 c.919-2A>G Knock-in Mice
To date, our laboratory had raised SLC26A4 c.919-2A>G knock-in mice. Morphologically, atrophy of the spiral ligament and stria vascularis was demonstrated. It also resulted in the changes of endocochlear potential and potassium concentration in the endolymph. Finally, it led to loss of the hair cells and hearing loss. In the present study, mice embryonic stem cells, neural progenitor cells and the inner ear differentiated cells were delivered into the cochlear of either SLC26A4 c.919-2A>G knock-in mice or the wild type B6 mice through direct injection via the round window membrane. In both groups, survival of the transplanted cells was found mainly in the scala tympani and some in the scala vestibuli two weeks later. There was no transplanted cell in the stria vascularis and the scala media. Auditory brainstem response thresholds were elevated after cell transplantation, and the thresholds right after the transplant surgery and those one week and two weeks later had no significant change.
Part II: Administration of Betamethasone Attenuates Intracochlear Cell Transplantation Trauma-induced Hearing Loss
After the intracochlear cell transplantation, the loss of the residual hearing develops. Application of glucocorticoid has been showed to ameliorate hearing loss resulting from the trauma of cochlear implantation in experimental animals. To investigate whether administration of the glucocorticoid can protect hearing, betamethasone of either 200 μg/ml or 800 μg/ml was injected into the cochlea of the B6 mice with the transplanted stem cells via the round window membrane simultaneously. Auditory brainstem responses (ABRs) were measured immediately, one week, and two weeks after the cell transplantation. The ABR thresholds increased right after the cell transplantation in both the control group and the betamethasone-treated group, and the hearing partially recovered in the treated group one week and two weeks after the surgery. Simultaneous injection of the betametasone of 800 μg/ml with the transplanted cell can significantly attenuate the hearing loss resulting from the trauma of intracochlear cell transplantation and is a novel strategy for preserving the residual hearing.
Subjects
stem cell
inner ear
genetic deafness mice
steroid treatment
Type
thesis
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