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To evaluate the effect of human adipose-derived stem cells (ASCs) on auditory neurons with respect to a potential application in cochlear implantation. Spiral ganglions from rats were enzymatically dissociated and cocultured with or without ASCs in a coculture system. After 24 and 48 h, inserts with ASCs were removed and the dissociated neurons were fixed and stained. Then, a cell count of all dissociated cells and neurons was performed and the length of the neurites was evaluated. The potential effect of ASCs on the direction of neurite outgrowth was evaluated in a chemotaxis assay. For this, one chamber of the assay was filled with ASCs in medium and the other chamber filled with medium only. After 48 h, the growth direction of neurite outgrowth was evaluated. Cocultivation of auditory neurons with ASCs resulted in a marked and statistically significant increase in neurite outgrowth at 24 and 48 h after plating. Moreover, the number of surviving neurons and the percentage of neurons among the dissociated cells were higher in the coculture group compared with the control group during both observation periods. However, this difference was statistically significant only at one time point. A directional outgrowth of the neurons was not observed. ASCs appear to enhance the survival and the neuritogenesis of auditory neurons. This might be of particular interest for cochlear implantation, in which a proper function of the auditory nerve with a sufficient number of neurons and surviving peripheral processes is essential.

The Brn3.1gene encodes for the protein Brn3.1, which is a member of the POU-IV class of transcription factors. Mutation leads to nonsyndromic human progressive hearing loss (DFNA15). To investigate the suitability of the Brn3.1promoter for Cre recombinase-induced genetic recombination in cochlear hair cells, we established a transgenic Brn3.1 Cre mouse. This mouse line was crossbred with floxed ROSA26lacZand ROSA26eYFPreporter mice. The cochleae were histologically analysed in cryosections at E16.5 and whole-mount preparations from P2 until P85. In addition, mice from all used strains and their recombinant offspring were tested electrophysiologically by auditory brainstem responses (ABR) and distorsion product otoacoustic emissions (DPOAE). Cre recombinase activity could be detected in P14 and P21 animals in a mosaic pattern in 26.3 and 9.9 of the outer hair cells, respectively. All investigated mice showed normal ABR and DPOAE values, indicating that neither insertion of the internal ribosome entry site (IRES) Cre cassette into the Brn3.1gene led to abnormal auditory development nor did the reporter strains show inherited hearing disorders. This study shows that Cre expression under the control of the Brn3.1promoter is feasible and that the insertion of the internal ribosome entry site Cre cassette into this locus exerted no effects on hearing development. Because of the inconstant pattern and the limited duration of expression, the application of the developed mouse line might be restricted. Also, the unchanged hearing capacity and structural integrity of the organ of Corti in available reporter lines indicate that they may be useful tools for hearing research.

Taurine is an ubiquitary expressed aminosulfonic acid known to play an important role in the development and maintenance of the nervous system. It is distributed in the inner ear, contributing toward the protection of hair cells against aminoglycoside-induced or bilirubin-induced ototoxicity. Thus, the question arises whether taurine also has an influence on the cellular integrity of the auditory neurons. To test this hypothesis, isolated cells of the spiral ganglion were cocultured with taurine or the neurotrophic factors brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) as controls. The analysis included cellular survival rate and neurite outgrowth. With application of taurine, the survival of glial cells and neurons was stimulated in a similar pattern, whereas BDNF and NT-3 only effected neuronal survival. Furthermore, administration of taurine resulted in enhanced neurite outgrowth comparable with the effect of the neurotrophic factors. These new insights on the neuromodulatory effects of taurine on auditory neurons suggest the use of this aminosulfonic acid to reduce the degeneration of auditory neurons in sensorineural hearing loss. Consecutively, a new therapeutical approach for the therapy of hearing impairment could be discussed.

The cochlear nucleus is the first relay station for acoustic information in the auditory pathway and its cellular integrity is affected by hearing loss. Neurotrophic factors, which are known to regulate fundamental processes in the brain, are expressed in the cochlear nucleus and are regulated by the changes in the stimulation. The aim of this study was to evaluate the effect of the neurotrophins Brain derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) and the neurotrophic factor Fibroblast growth factor 2 (FGF2) on primary cultured cells of the mouse cochlear nucleus. No effect on overall cell growth was detected after 8 days in culture by the factors applied. NT-3 had a strong impact on enhancement of neuronal survival, whereas BDNF stimulated neuronal survival and axonal outgrowth. Axonal branching was negatively affected by the administration of BDNF. FGF2 did not show any effect. The results presented represent fundamental research on auditory neurons, but might be one step toward defining novel therapeutic strategies in the future to prevent cochlear nucleus degeneration induced by hearing loss.

To describe a technique for the intraoperative monitoring of residual hearing during a cochlear implant (CI) procedure and, thus, to identify the time of occurrence and surgical steps leading to hearing loss.

After surgery, wound healing begins with a well-orchestrated integration of several cytokines, cells, and extracellular matrix. Some studies show an involvement of stem cells in wound healing. However, little is known about the mechanism that leads to the migration of stem cells. Wound fluid (WF) with its cytokines may play an important role. We investigated in the present study the in vitroeffects of WF on adipose-derived stem cells (ADSCs). Survival, proliferation, structural integrity, changes in the multidifferentiation potential, and surface markers (cluster of differentiation [CD] 105, CD73, CD90) of ADSCs after cultivation with WF was analyzed. Further, the migration effect of WF on ADSCs was evaluated. The proliferation rate and the migration potential of ADSCs were enhanced significantly by cultivation with WF. There was also a change in the quantity of surface markers after cultivation with WF. In conclusion, in vitroexpansion of stem cells with WF proved possible. WF and its cytokines could represent one primary reason for the migration of stem cells toward the wound. Future investigation is warranted to clarify the significance of the shift in surface markers.

The 5-year survival rate of patients suffering from head and neck squamous cell carcinoma (HNSCC) is unsatisfying despite the advances in carcinoma treatment. Recent studies suggest that stem cells can be used as a gene therapy carrier for cancer treatment. Stem cells produce different cytokines such as growth factors in a paracrine manner and cancer cells may show drug resistance in the presence of such growth factors. Reports in the literature concerning treatment of cancer using bone marrow derived stem cells (BMSC) are controversial, which led us to investigate the effects of paclitaxel on human HNSCC cell lines (FaDu and HLaC 78) cultivated simultaneously with BMSC in a transwell system (co-culture). Co-culture and HNSCC cell lines were treated with 10nM of paclitaxel for 24h. Morphology, viability and apoptosis were measured by microscopy, the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the Annexin V-propidium iodide test. The survival of HNSCC cell lines treated with paclitaxel in co-culture increased significantly compared to control cells. Apoptosis of HNSCC cell lines in co-culture was attenuated significantly. In conclusion, BMSC increase HNSCC resistance to treatment with paclitaxel in vitro. Tumor-stroma interactions are critical components of tumor biology including tumor invasion and metastatic potential. Therefore particular attention must be paid to the complex tumor-stroma interactions to fully understand how tumor cells become chemoresistant.

To describe a technique enabling the intraoperative assessment of the mechanical coupling of active middle ear implants in patients with normal or dysfunctional middle ears.

To assess the variance in cochlear implant electrode insertion depth in degrees around the modiolus (angular insertion depth) in free-fitting and perimodiolar electrode arrays.

Objective:To assess intracochlear trauma using two different round window‐related cochleostomy techniques in human temporal bones.

Background: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups.

Objective/Hypothesis:The objective of this controlled animal study was to evaluate the effects of intrascalar blood on hearing.

The aim of this report was to examine basal trauma in implanted human temporal bones and discuss modified approaches to the basal cochlear turn to avoid destruction of basal cochlear structures. Thirty-three human temporal bones were implanted with four different cochlear implant electrode arrays manufactured by MED-EL using either a caudal approach cochleostomy or round window membrane insertions. All specimens were processed with a special histological technique that allows sectioning of undecalcified bone with the electrode in situ. All bones were evaluated histologically in terms of basal cochlear trauma. Two pathomechanisms of basal trauma could be distinguished and were evaluated separately, buckling of the basal end of the array and trauma by drilling. Using the caudal approach cochleostomy, the total percentage of destructive basal trauma was 48% compared to less than 15% when performing round window membrane insertions. Although it is still unclear whether basal cochlear trauma influences apical cochlear function or not, adapted surgical procedures and no forceful insertion maneuvers should be used when performing cochlear implantations with hearing preservation.