Andreas Radeloff

Variance of Angular Insertion Depths in Free-Fitting and Perimodiolar Cochlear Implant Electrodes

Objective: 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. Materials and Methods: Twenty-eight fresh human temporal bones were implanted with free-fitting cochlear implant electrodes, and 18 bones were implanted using perimodiolar electrode arrays. Specimens were embedded, and 2-dimensional radiographs were obtained to assess angular insertion depths. Histologic serial sections of undecalcified bones were then evaluated to analyze intracochlear electrode positions. Finally, linear surgical insertion depths (in millimeters) were correlated with angular insertion depth (degrees around the modiolus). Results: A moderate variance of angular insertion depth was documented for both free-fitting and perimodiolar electrode arrays. Full insertions into the scala tympani ranged from 540 to 630 degrees with free-fitting arrays and from 270 to 375 degrees with perimodiolar electrodes. In free-fitting devices, a linear relationship between linear (in millimeters) and angular (degrees) insertion depths was observed. Insertions into scala vestibuli were observed in 9 of 28 and 5 of 18 of the specimens for free-fitting and perimodiolar electrodes, respectively. Additionally, scala vestibuli insertions showed greater angular insertion depths when compared with scala tympani implantations. Conclusion: Variances in angular insertion depths seem to be moderate and similar in free-fitting and perimodiolar electrode arrays. Scala vestibuli insertions showed greater angular insertion depths than comparable insertions into the scala tympani. In perimodiolar electrodes, angular insertion depths equal or greater than 390 degrees suggested scala vestibuli placement.

Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro

Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 μM and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells.

Chromosomal aberrations and deoxyribonucleic acid single-strand breaks in adipose-derived stem cells during long-term expansion in vitro

BACKGROUND AIMS Adipose-derived stem cells (ASCs) are a promising mesenchymal cell source for tissue engineering approaches. To obtain an adequate cell amount, in vitro expansion of the cells may be required in some cases. To monitor potential contraindications for therapeutic applications in humans, DNA strand breaks and chromosomal aberrations in ASCs during in vitro expansion were examined. METHODS After isolation of ASC from human lipoaspirates of seven patients, in vitro expansion over 10 passages was performed. Cells from passages 1, 2, 3, 5 and 10 were used for the alkaline single-cell microgel electrophoresis (comet) assay to detect DNA single-strand breaks and alkali labile as well as incomplete excision repair sites. Chromosomal changes were examined by means of the chromosomal aberration test. RESULTS During in vitro expansion, ASC showed no DNA single-strand breaks in the comet assay. With the chromosomal aberration test, however, a significant increase in chromosomal aberrations were detected. CONCLUSIONS The study showed that although no DNA fragmentation could be determined, the safety of ASC cannot be ensured with respect to chromosome stability during in vitro expansion. Thus, reliable analyses for detecting ASC populations, which accumulate chromosomal aberrations or even undergo malignant transformation during extensive in vitro expansion, must be implemented as part of the safety evaluation of these cells for stem cell-based therapy.

A coated electrode carrier for cochlear implantation reduces insertion forces.

To assess the insertion forces and feasibility of insertion of a prototype electrode carrier coated with a flexible and biodegradable coating developed for lubrication and drug delivery.

Bisphosphonate-induced osteonecrosis of the external ear canal: a retrospective study

In 2003, osteonecrosis of the jaw was described as an intraoral complication of bisphosphonate therapy. More recently, cases of avascular necrosis of the hip were reported in patients with long-lasting bisphosphonate therapy. Thus, it was the aim of the present study to analyze cases of benign osteonecrosis of the external ear canal and to retrospectively identify a possible relationship to long-lasting bisphosphonate therapy. 13 patients with osteonecrosis of the external ear canal operated on between 2005 and 2009 were included. Patient histories were reviewed for possible previous or current bisphosphonate therapy. Three patients with osteonecrosis of the external ear canal and long-term bisphosphonate therapy could be identified. They had been treated either for breast cancer or multiple myeloma. Certainly, the jaw is an area of increased risk for developing osteonecrosis with its high mechanical stress and intraoral bacterial flora. However, osteonecrosis of the hips and the external ear canal in patients receiving long-term bisphosphonate therapy necessitate further investigation of a possible systemic, bisphosphonate-related phenomenon.

Isolation and characterization of neural stem cells from the neonatal rat cochlear nucleus

Neural stem cells have been identified in multiple parts of the postnatal mammalian brain, as well as in the inner ear. No investigation of potential neural stem cells in the cochlear nucleus has yet been performed. The aim of this study was to investigate potential neural stem cells from the cochlear nucleus by neurosphere assay and in histological sections to prove their capacity for self-renewal and for differentiation into progenitor cells and cells of the neuronal lineage. For this purpose, cells of the cochlear nucleus of postnatal day 6 rats were isolated and cultured for generation of primary neurospheres. Spheres were dissociated and cells analyzed for capacity for mitosis and differentiation. Cell division was detected by cell-counting assay and BrdU incorporation. Differentiated neural progenitor cells showed distinct labeling for Nestin and for Atoh1. Positive staining of ß-III Tubulin, glial fibrillary acid protein (GFAP) and myelin basic protein (MBP) showed differentiation into neurons, astrocytes and oligodendrocytes. Furthermore, Nestin- and BrdU-labeled cells could also be detected in histological sections. In conclusion, the isolated cells from the cochlear nucleus presented all the features of neural stem cells: cell division, presence of progenitor cells and differentiation into different cells of the neuronal lineage. The existence of neural stem cells may add to the understanding of developmental features in the cochlear nucleus.

A hydrogel coating for cochlear implant arrays with encapsulated adipose-derived stem cells allows brain-derived neurotrophic factor delivery

Abstract Conclusion: Human adipose-derived stem cells (ASCs), encapsulated in a fibrin-collagen hydrogel for the coating of an electrode array, produce sufficient amounts of neurotrophic factors and may be suitable for enhancing the bioelectric interface of cochlear implants (CIs). Objectives: To evaluate different hydrogel compositions loaded with ASCs with regard to delivery of neuroactive substances and mechanical suitability for the coating of a CI electrode array. Methods: ASCs were cultivated in hydrogels consisting of collagen and fibrin in varying fractions (0:1, 1:1, 1:2, and 1:0). The cell proliferation and viability, as well as the production of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and laminin were determined. Two hydrogel compositions were used as a coating for CI electrode arrays and tested in a scala tympani model. Results: Cell proliferation was best in collagen/fibrin hydrogel compositions (1:1 and 1:2) and increasing amounts of BDNF (up to 2.59 ng/ml) and laminin (up to 320 ng/ml) were detected. GDNF production was inconsistent and markedly lower. A sufficient coating of a CI electrode carrier in terms of stability and flexibility was achieved only with mixed compositions, although hydrogels formed bulky and uneven layers on the silicone surfaces.

Multipotent Stromal Cells for Autologous Cell Therapy Approaches in the Guinea Pig Model

Multipotent stromal cells have become of increasing interest due to their potential to provide therapeutic approaches for autologous tissue repair. However, these cells are not well defined in the guinea pig, which represents an important model in hearing research. Adipose-tissue-derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) were isolated from different donor sites, and growth curves were generated to judge the proliferation potential. Adipogenic, chondrogenic and osteogenic differentiation was induced and confirmed histologically. Finally, the capability of guinea pig ADSC to differentiate into neuron-like cells was investigated. With regard to the expansion potential, total cell number and doubling time, ADSC from the neck were the most suitable cells of the tested donor sites. Both ADSC and BMSC showed nearly identical behaviour and ability to undergo multilineage differentiation. Thus, we identified ADSC from the neck as a promising cell source for autologous cell-based approaches in hearing research using the guinea pig model.

Growth behavior of cochlear nucleus neuronal cells on semiconductor substrates.

Auditory brainstem implants provide sound information by direct stimulation of the cochlear nucleus to patients with dysfunctional or absent cranial nerve VIII. In contrast to patients with cochlear implants, the use of the auditory brainstem implants is less successful. This cannot be fully explained by the difference location of stimulation but a rather unspecific neuronal stimulation. The aim of this study was to further examine neuronal cells of the cochlear nucleus and to test their interactions with semiconductor substrates as a potential electrode material for improved auditory brainstem implants. The cochlear nuclei of postnatal day 7 rats were microsurgically dissected. The tissue was dissociated enzymatically and plated on coverslips as control and on the semiconductor substrates silicon or silicon nitride. After 4 days in culture the morphology and growth of dissociated cells was determined by fluorescence and scanning electron microscopy. Dissociated cells of the cochlear nucleus showed reduced cell growth on semiconductor substrates compared with controls. SEM analysis demonstrated close contact of neurons with supporting cells in culture and good adherence of neuronal growth cones on the used materials. These findings present basic knowledge for the development of neuron-electrode interfaces for future auditory brainstem implants.

Quality standards for bone conduction implants

Abstract Conclusion: Bone conduction implants are useful in patients with conductive and mixed hearing loss for whom conventional surgery or hearing aids are no longer an option. They may also be used in patients affected by single-sided deafness. Objectives: To establish a consensus on the quality standards required for centers willing to create a bone conduction implant program. Method: To ensure a consistently high level of service and to provide patients with the best possible solution the members of the HEARRING network have established a set of quality standards for bone conduction implants. These standards constitute a realistic minimum attainable by all implant clinics and should be employed alongside current best practice guidelines. Results: Fifteen items are thoroughly analyzed. They include team structure, accommodation and clinical facilities, selection criteria, evaluation process, complete preoperative and surgical information, postoperative fitting and assessment, follow-up, device failure, clinical management, transfer of care and patient complaints.