[Rehabilitation with cochlear implants in children with malformations of the inner ear]. / Cochleaimplantatversorgung von Kindern mit Malformationen des Innenohrs.

Cochlear implants (CIs) are the treatment of choice for hearing rehabilitation in children with congenital or acquired profound hearing loss or deafness in order to ensure appropriate speech development and avoid social deprivation. However, in the case of a radiologically detectable malformation of the inner ear structures and potentially associated hypo- or aplasia of the vestibulocochlear nerve, application of a CI is either not possible, or the functional outcome may be of limited predictability. In addition, the risk of surgical complications is also increased in these patients. Counseling parents and developing an appropriate individual therapeutic decision can therefore be a major challenge for the medical team. The current paper is intended to provide support in this regard. It presents criteria for various inner ear malformations and discusses possible treatment options.

A retrospective European multicenter analysis of the functional outcomes after active middle ear implant surgery using the third generation vibroplasty couplers.

PURPOSE: To evaluate the safety and performance of three novel vibroplasty couplers that allow attachment of the floating mass transducer of a transcutaneous active middle ear implant (AMEI) to the round window (RW) membrane, the long process (LP), or the incus body and the short process (SP) of the incus. METHODS: Retrospective multicenter cohort study of 25 AMEI users with sensorineural or mixed hearing loss that were among the first implanted with an AMEI vibrating ossicular prosthesis in combination with the third generation of vibroplasty couplers between 2014 and 2016. Main Outcome Measures were bone-conduction pure-tone and vibroplasty thresholds, postoperative aided sound field thresholds and postoperative aided word recognition score (WRS). RESULTS: Bone conduction threshold changes of more than 10 dB in 4PTABC were observed in two subjects. A mean improvement of 57.8% in speech recognition was observed with a mean WRS at 65 dB SPL improving from 14.8% (SD 21.9%) preoperatively to a mean aided score of 72.6% (SD 18.6%). Sound field thresholds improved from an average 4PTASF of 64.1 dB HL (SD 9.8 dB HL) to 37.0 dB HL (SD 8.9 dB HL), resulting in a mean functional gain of 27.1 dB. There was no significant difference in WRS or functional gain between the coupler types. CONCLUSION: Initial experience shows that all three third generation vibroplasty couplers represent safe and efficient attachment options for the FMT allowing the surgeon to choose the coupling type based on the present pathology.

Bilateral cochlear implantation is regarded as very beneficial: results from a worldwide survey by online questionnaire.

PURPOSE: Bilateral cochlear implant (CI) provision is now widely regarded as the most beneficial hearing intervention for acceptable candidates. This study sought to determine if a number of well-regarded hearing professionals at highly reputable clinics shared similar practices and beliefs regarding bilateral CI provision, use, and rehabilitation in children and adults. METHODS: An 11-question online questionnaire was created and distributed to all 27 clinics in the HEARRING group. Questions 1-5 asked for facts; questions 6-11 asked for opinions. RESULTS: 20 completed questionnaires were returned. All 20 respondents reported that their clinics perform bilateral cochlear implantation in children; 18 do so in adults. Regarding the fact-based questions, bilateral CI provision is more commonly performed and more likely to be reimbursed in children than in adults. Children are also much more likely to be implanted simultaneously than are adults. Regarding the opinion-based questions, respondents gave broadly similar answers. Communication between the CIs and speech coding strategies specifically developed for bilateral CI users were regarded as the two future technologies that would most enhance the benefit of bilateral CI use. CONCLUSIONS: Most clinics in the HEARRING group are very familiar with bilateral CI provision and hold similar opinions on its results and benefits. Hopefully the results described herein will lead to a greater acceptance and regular reimbursement of bilateral CI provision, especially in adults.

Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

BACKGROUND: A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. METHODS: We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. RESULTS: In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. DISCUSSION/CONCLUSION: ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival.

Device optimised chirp stimulus for ABR measurements with an active middle ear implant.

OBJECTIVE: Active middle ear implants are widely used to treat adults and children with sensorineural, conductive, or mixed hearing loss. Currently, there is no adequate method to determine the performance of active middle ear implant systems. DESIGN: The proposed method is based on measuring the auditory brainstem response while stimulating the hearing system via the active middle ear implant (Vibrant SoundbridgeTM, VSB; MEDEL, Austria). The acoustic stimulation was achieved via an optimised chirp stimulus (CE-Chirp), implemented in the Eclipse system (Interacoustics, Denmark). To compensate for the frequency-specific delays in the VSB system, the underlying model function of the CE-Chirp was adjusted accordingly (VSB-CE-Chirp). Study samples: The study includes 12 subjects having mild to profound sensorineural, conductive or mixed hearing loss. RESULTS: The use of an optimised VSB-CE-Chirp instead of the CE-Chirp increases significantly the ABR wave V amplitudes (1.63 times) and so also increases their identifiability (by 15.2%). On average, wave V could be identified at a 7.5 dB lower stimulation level. CONCLUSION: The constructed VSB-CE-Chirp stimulus, after it had been transmitted through the VSB system, follows well the shape of the original CE-Chirp. Preliminary measurements in VSB patients demonstrated a significantly improved ABR amplitude with the VSB-CE-Chirp.

Plasma-assisted hydrophilization of cochlear implant electrode array surfaces enables adhesion of neurotrophin-secreting cells.

OBJECTIVE: To evaluate plasma treatment for enhancing the biocompatibility of cochlear implant (CI) silicone surfaces, thus allowing colonization with human adipose-derived stem cells (hASCs) that are known to provide neurotrophic support. METHODS: Silicone samples and CI electrode arrays were treated with 4 low-pressure plasmas of different characteristics. The hydrophilicity of plasma-treated and control surfaces as well as the adherence and morphology of hASCs were assessed. Finally, the insertion forces of electrode arrays were determined and the colonization potential of the electrode arrays with hASCs were tested. RESULTS: The hydrophilicity of the silicone surfaces was significantly enhanced after plasma treatment, as was the adherence of hASCs. The characteristic morphology of hASCs was observed when grown on plasma-treated but not on untreated silicone surfaces. The insertion forces of plasma-treated electrode arrays were similar to those of untreated arrays, and the colonization of plasma-treated electrode arrays with hASCs was feasible. CONCLUSION: Plasma treatment of CI electrode arrays enhances their biocompatibility and allows for the colonization with hASCs that are known to produce neurotrophic factors.

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.

Dynamic changes of the neurogenic potential in the rat cochlear nucleus during post-natal development.

Neuronal stem cells have been described in the post-natal cochlear nucleus recently. The aim of the study was to analyse the neurogenic potential in the cochlear nucleus from the early post-natal days until adulthood. Cochlear nuclei from Sprague-Dawley rats from post-natal day P3 up to P40 were examined. Neurosphere assays showed persistent neurosphere formation from the early post-natal days until adulthood. The numbers of generated neurospheres were fewer in older ages. Neurospheres were smaller, but displayed the same pattern of neuronal stem cell markers. The markers GFAP, MBP and ß-III Tubulin showed differentiation of dissociated cells from the neurospheres in all cells of the neuronal lineage. BrdU incorporation could be detected, in an age-dependent decrease, in whole-mount experiments of the cochlear nucleus on all examined days. BrdU co-labelled with Atoh1 and ß-III Tubulin. In addition, gene expression and cellular distribution studies of the neuronal stem cell markers displayed an age-dependent reduction in both quantity and numbers. The presented results display a possible neurogenic potential until adulthood in the cochlear nucleus by in vitro and in vivo experiments. The fact that this potential is highest at a critical period of development reveals possible functional importance for the development of the cochlear nucleus and the auditory function. The persistent neurogenic potential displayed until adulthood could be a neurogenic niche in the adult cochlear nucleus, which might be used for potential therapeutic strategies.

Co-Occurrence of EBV-Positive Mucocutaneous Ulcer (EBV-MCU) and CLL/SLL in the Head and Neck Region.

EBV-positive mucocutaneous ulcer (EBV-MCU) was classified as a rare new entity of the lymphoproliferative B-cell diseases by the WHO in 2017 and must be distinguished from head and neck squamous cell carcinoma by early biopsy. The aim of the study is to raise awareness of the disease and to give a review of the current literature and a recommendation for EBV-MCU management. All EBV-MCU cases of the head and neck region published so far were included. We also report a case of a pharyngeal EBV-MCU in an 89-year-old patient who was immunosuppressed by chronic lymphatic leukaemia/small lymphocytic lymphoma (CLL/SLL). In contrast to all previously described cases, histopathology showed a co-infiltration of EBV-MCU and CLL/SLL. A total of 181 cases were identified on PubMed and summarised. EBV-MCU was predominantly caused by immunosuppressive drug therapy. Complete remission could be achieved in 68% of cases and was mainly attributed to a reduction of the immunosuppressive therapy alone (72%). However, some severe cases require more aggressive treatment. Regarding the various histopathologic similarities to other lymphoproliferative disorders, the diagnosis of EBV-MCU can be misleading, with a great impact on patient care and treatment. This diagnosis must be made with caution and requires a combination of clinical, morphological and immunophenotypic features.

The Otoprotective Effect of Ear Cryotherapy: Systematic Review and Future Perspectives.

This systematic review investigates ear cooling and cryotherapy in the prevention and treatment of inner ear damage and disease, within the context of animal models and clinical studies. A literature search was carried out in the databases Pubmed and Cochrane Library. Ten studies were identified concerning the otoprotective properties of cryotherapy. Nine of these were rodent in vivo studies (mice, rats, gerbils, guinea pigs). One study involved human subjects and investigated cryotherapy in idiopathic sensorineural hearing loss. The studies were heterogeneous in their goals, methods, and the models used. Disorder models included ischemia and noise damage, ototoxicity (cisplatin and aminoglycoside), and CI-electrode insertion. All ten studies demonstrated significant cryotherapeutic otoprotection for their respective endpoints. No study revealed or expressly investigated otodestructive effects. While limited in number, all of the studies within the scope of the review demonstrated some degree of cryotherapeutic, otoprotective effect. These promising results support the conducting of further work to explore and refine the clinical applicability and impact of cryotherpeutics in otolaryngology.

Challenging Times for Cochlear Implant Users - Effect of Face Masks on Audiovisual Speech Understanding during the COVID-19 Pandemic.

Unhindered auditory and visual signals are essential for a sufficient speech understanding of cochlear implant (CI) users. Face masks are an important hygiene measurement against the COVID-19 virus but disrupt these signals. This study determinates the extent and the mechanisms of speech intelligibility alteration in CI users caused by different face masks. The audiovisual German matrix sentence test was used to determine speech reception thresholds (SRT) in noise in different conditions (audiovisual, audio-only, speechreading and masked audiovisual using two different face masks). Thirty-seven CI users and ten normal-hearing listeners (NH) were included. CI users showed a reduction in speech reception threshold of 5.0 dB due to surgical mask and 6.5 dB due to FFP2 mask compared to the audiovisual condition without mask. The greater proportion of reduction in SRT by mask could be accounted for by the loss of the visual signal (up to 4.5 dB). The effect of each mask was significantly larger in CI users who exclusively hear with their CI (surgical: 7.8 dB, p = 0.005 and FFP2: 8.7 dB, p = 0.01) compared to NH (surgical: 3.8 dB and FFP2: 5.1 dB). This study confirms that CI users who exclusively rely on their CI for hearing are particularly susceptible. Therefore, visual signals should be made accessible for communication whenever possible, especially when communicating with CI users.

How Face Masks Interfere With Speech Understanding of Normal-Hearing Individuals: Vision Makes the Difference.

OBJECTIVE: To investigate the effects of wearing a simulated mask on speech perception of normal-hearing subjects. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: Fifteen normal-hearing, native German speakers (8 female, 7 male). INTERVENTION: Different experimental conditions with and without simulated face masks using the audiovisual version of the female German Matrix test (Oldenburger Satztest, OLSA). MAIN OUTCOME MEASURES: Signal-to-noise ratio (SNR) at speech intelligibility of 80%. RESULTS: The SNR at which 80% speech intelligibility was achieved deteriorated by a mean of 4.1 dB SNR when simulating a medical mask and by 5.1 dB SNR when simulating a cloth mask in comparison to the audiovisual condition without mask. Interestingly, the contribution of the visual component alone was 2.6 dB SNR and thus had a larger effect than the acoustic component in the medical mask condition. CONCLUSIONS: As expected, speech understanding with face masks was significantly worse than under control conditions. Thus, the speaker's use of face masks leads to a significant deterioration of speech understanding by the normal-hearing listener. The data suggest that these effects may play a role in many everyday situations that typically involve noise.

Expert validation of prediction models for a clinical decision-support system in audiology.

For supporting clinical decision-making in audiology, Common Audiological Functional Parameters (CAFPAs) were suggested as an interpretable intermediate representation of audiological information taken from various diagnostic sources within a clinical decision-support system (CDSS). Ten different CAFPAs were proposed to represent specific functional aspects of the human auditory system, namely hearing threshold, supra-threshold deficits, binaural hearing, neural processing, cognitive abilities, and a socio-economic component. CAFPAs were established as a viable basis for deriving audiological findings and treatment recommendations, and it has been demonstrated that model-predicted CAFPAs, with machine learning models trained on expert-labeled patient cases, are sufficiently accurate to be included in a CDSS, but it requires further validation by experts. The present study aimed to validate model-predicted CAFPAs based on previously unlabeled cases from the same data set. Here, we ask to which extent domain experts agree with the model-predicted CAFPAs and whether potential disagreement can be understood in terms of patient characteristics. To these aims, an expert survey was designed and applied to two highly-experienced audiology specialists. They were asked to evaluate model-predicted CAFPAs and estimate audiological findings of the given audiological information about the patients that they were presented with simultaneously. The results revealed strong relative agreement between the two experts and importantly between experts and the prediction for all CAFPAs, except for the neural processing and binaural hearing-related ones. It turned out, however, that experts tend to score CAFPAs in a larger value range, but, on average, across patients with smaller scores as compared with the machine learning models. For the hearing threshold-associated CAFPA in frequencies smaller than 0.75 kHz and the cognitive CAFPA, not only the relative agreement but also the absolute agreement between machine and experts was very high. For those CAFPAs with an average difference between the model- and expert-estimated values, patient characteristics were predictive of the disagreement. The findings are discussed in terms of how they can help toward further improvement of model-predicted CAFPAs to be incorporated in a CDSS for audiology.

Considerations for Fitting Cochlear Implants Bimodally and to the Single-Sided Deaf.

When listening with a cochlear implant through one ear and acoustically through the other, binaural benefits and spatial hearing abilities are generally poorer than in other bilaterally stimulated configurations. With the working hypothesis that binaural neurons require interaurally matched inputs, we review causes for mismatch, their perceptual consequences, and experimental methods for mismatch measurements. The focus is on the three primary interaural dimensions of latency, frequency, and level. Often, the mismatch is not constant, but rather highly stimulus-dependent. We report on mismatch compensation strategies, taking into consideration the specific needs of the respective patient groups. Practical challenges typically faced by audiologists in the proposed fitting procedure are discussed. While improvement in certain areas (e.g., speaker localization) is definitely achievable, a more comprehensive mismatch compensation is a very ambitious endeavor. Even in the hypothetical ideal fitting case, performance is not expected to exceed that of a good bilateral cochlear implant user.

Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events.

Background and Objective: The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process. Methods: A systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types. Results: A total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4-6.6%) of ETFO, 28.6% (26.6-30.6%) of ESD, and 0.53% (0.2-1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1-1.3%), 11% (9.2-13.0%), and 3.2% (2.5-3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed. Conclusion: Considering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications.

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.

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.

Protection of inner ear function after cochlear implantation: compound action potential measurements after local application of glucocorticoids in the guinea pig cochlea.

BACKGROUND: Cochlear implant users with residual hearing often benefit greatly from simultaneous electric and acoustic stimulation. However, implantation can cause trauma to the inner ear, resulting in poorer hearing postoperatively. We investigated whether a single local injection of glucocorticoids can reduce hearing loss in long-term implanted guinea pigs. METHODS: Three groups of animals underwent bilateral surgery. One ear was implanted with an electrode, and the contralateral ear received a cochleostomy only. A single dose of the glucocorticoids triamcinolone or dexamethasone, or of artificial perilymph was infused into cochleae via cochleostomy. Compound action potentials were measured before and after application and for 3 months postoperatively. Tissue growth was measured as the percentage of the total area of the scala tympani that was obliterated. RESULTS: Ears subjected to cochleostomy only and treated with glucocorticoids demonstrated a mild hearing loss. In the implanted ears, both glucocorticoids preserved hearing at least temporarily. The volume of tissue growth within the scala tympani was not reduced, and there was no relation between the amount of tissue and hearing loss. CONCLUSIONS: Both glucocorticoids show a potential benefit for hearing preservation in implanted ears. Glucocorticoid therapy may be useful to protect residual hearing during cochlear implantation.

Differentiation Behaviour of Adipose-Derived Stromal Cells (ASCs) Seeded on Polyurethane-Fibrin Scaffolds In Vitro and In Vivo.

Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation.

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects.