BackgroundAdult mesenchymal stem cells (MSCs) derived from adipose tissue have the capacity to differentiate into mesenchymal as well as endodermal and ectodermal cell lineage in vitro. We characterized the multipotent ability of human adipose tissue-derived stem cells (hADSCs) as MSCs and investigated the neural differentiation potential of these cells.ResultsHuman ADSCs from earlobe fat maintained self-renewing capacity and differentiated into adipocytes, osteoblasts, or chondrocytes under specific culture conditions. Following neural induction with bFGF and forskolin, hADSCs were differentiated into various types of neural cells including neurons and glia in vitro. In neural differentiated-hADSCs (NI-hADSCs), the immunoreactivities for neural stem cell marker (nestin), neuronal markers (Tuj1, MAP2, NFL, NFM, NFH, NSE, and NeuN), astrocyte marker (GFAP), and oligodendrocyte marker (CNPase) were significantly increased than in the primary hADSCs. RT-PCR analysis demonstrated that the mRNA levels encoding for ABCG2, nestin, Tuj1, MAP2, NFL, NFM, NSE, GAP43, SNAP25, GFAP, and CNPase were also highly increased in NI-hADSCs. Moreover, NI-hADSCs acquired neuron-like functions characterized by the display of voltage-dependent tetrodotoxin (TTX)-sensitive sodium currents, outward potassium currents, and prominent negative resting membrane potentials under whole-cell patch clamp recordings. Further examination by RT-PCR showed that NI-hADSCs expressed high level of ionic channel genes for sodium (SCN5A), potassium (MaxiK, Kv4.2, and EAG2), and calcium channels (CACNA1C and CACNA1G), which were expressed constitutively in the primary hADSCs. In addition, we demonstrated that Kv4.3 and Eag1, potassium channel genes, and NE-Na, a TTX-sensitive sodium channel gene, were highly induced following neural differentiation.ConclusionsThese combined results indicate that hADSCs have the same self-renewing capacity and multipotency as stem cells, and can be differentiated into functional neurons using bFGF and forskolin.

The use of PRP and/or nMSCs promotes facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

Objective: Superficial siderosis (SS) of the CNS is associated with cerebellar ataxia, sensorineural hearing loss, and pyramidal symptoms, which result from iron depositions on CNS surfaces. SS can produce bilateral vestibulopathy as the vestibulo-cochlear nerve is particularly vulnerable. To our knowledge, however, vestibular dysfunction in SS has not been reported thoroughly in the literature. Here, we describe a case of bilateral vestibulopathy, documented quantitatively by the video head impulse test (vHIT), in a patient with SS. Patient: A 60-year-old man presented with slowly progressing bilateral hearing loss, oscillopsia, and a severe gait disturbance that worsened in the dark. Intervention: After noticing deficits in the bedside head impulse test in all six semicircular canals, the patient underwent vHIT and brain MRI. Main Outcome Measure: MRI demonstrated a rim of hypointensities and signal losses in T2-weighted and gradient echo images around the cerebellum, brainstem, and vestibulo-cochlear nerve, which were compatible with an SS diagnosis. In addition, vHIT revealed reduced vestibuleocular reflex (VOR) gains, and abnormal catch-up saccades (both covert and overt saccades) in all semicircular canals. Results: The vHIT showed impaired VOR gains that were 0.55, 0.59, and 0.45 in the horizontal, anterior, and posterior canals, respectively. Conclusion: SS may result in chronic bilateral vestibulopathy with SNHL. Bilateral vestibulopathy originated peripherally in our participant, without cerebellar dysfunctions such as those reported in the literature. vHIT findings have not been previously reported in patients with SS, and our study suggests that vHIT is a useful tool to document vestibular dysfunction.

The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We established the auditory neuropathy guinea pig model using 1 mM ouabain application to the round window niche. After application of ouabain to the round window niche, degeneration of most spiral ganglion neurons (SGNs) without the loss of hair cells within the organ of Corti and increasing the auditory brain responses (ABR) threshold were found. After transplantation of neural differentiated hMSCs, the number of SGNs was increased, and some of the SGNs expressed immunoreactivity with human nuclear antibody under confocal laser scanning microscopy. ABR results showed mild hearing recovery after transplantation. Based on an auditory neuropathy animal model, these findings suggest that it may be possible to replace degenerated SGNs by grafting stem cells into the scala tympani.

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rMasseter and tMasseter were useful as anatomic landmarks to differentiate a parotid deep lobe tumour from a superficial lobe tumour.

ObjectivesIn mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae.MethodsHMSCs were isolated from the bone marrow which was obtained from the mastoid process during mastoidectomy for ear surgery. Following neural induction with basic fibroblast growth factor and forskolin, we studied the several neural marker and performed electrophysiological analysis. NI-hMSCs were transplanted into the neomycin treated deafened guinea pig cochlea. Engraftment of NI-hMSCs was evaluated immunohistologically at 8 weeks after transplantation.ResultsFollowing neural differentiation, hMSCs expressed high levels of neural markers, ionic channel markers, which are important in neural function, and tetrodotoxin-sensitive voltage-dependent sodium currents. After transplantation into the scala tympani of damaged cochlea, NI-hMSCs-injected animals exhibited a significant increase in the number of SGNs compared to Hanks balanced salt solution-injected animals. Transplanted NI-hMSCs were found within the perilymphatic space, the organ of Corti, along the cochlear nerve fibers, and in the spiral ganglion. Furthermore, the grafted NI-hMSCs migrated into the spiral ganglion where they expressed the neuron-specific marker, NeuN.ConclusionThe results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24 h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (K + F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to K + F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.