ABSTRACT
Hyperbaric oxygen therapy (HBOT) is a noninvasive widely applied treatment that increases the oxygen pressure in tissues. In cochlear implant (CI) research, intracochlear application of neurotrophic factors (NTFs) is able to improve survival of spiral ganglion neurons (SGN) after deafness. Cell-based delivery of NTFs such as brain-derived neurotrophic factor (BDNF) may be realized by cell-coating of the surface of the CI electrode. Human mesenchymal stem cells (MSC) secrete a variety of different neurotrophic factors and may be used for the development of a biohybrid electrode in order to release endogenously-derived neuroprotective factors for the protection of residual SGN and for a guided outgrowth of dendrites in the direction of the CI electrode. HBOT could be used to influence cell behaviour after transplantation to the inner ear. The aim of this study was to investigate the effect of HBOT on the proliferation, BDNF-release and secretion of neuroprotective factors. Thus, model cells (an immortalized fibroblast cell line (NIH3T3)-native and genetically modified) and MSCs were repeatedly (3 x - 10 x) exposed to 100% oxygen at different pressures. The effects of HBO on cell proliferation were investigated in relation to normoxic and normobaric conditions (NOR). Moreover, the neuroprotective and neuroregenerative effects of HBO-treated cells were analysed by cultivation of SGN in conditioned medium. Both, the genetically modified NIH3T3/BDNF and native NIH3T3 fibroblasts, showed a highly significant increased proliferation after five days of HBOT in comparison to normoxic controls. By contrast, the number of MSCs was decreased in MSCs treated with 2.0 bar of HBO. Treating SGN cultures with supernatants of fibroblasts and MSCs significantly increased the survival rate of SGN. HBO treatment did not influence (increase / reduce) this effect. Secretome analysis showed that HBO treatment altered the protein expression pattern in MSCs.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Hyperbaric Oxygenation , Neuroprotection/physiology , Animals , Brain-Derived Neurotrophic Factor/genetics , Cell Proliferation/physiology , Cell Survival/physiology , Cell- and Tissue-Based Therapy , Culture Media, Conditioned , Female , Gene Expression Profiling , Humans , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Mice , NIH 3T3 Cells/metabolism , NIH 3T3 Cells/transplantation , Nerve Regeneration/physiology , Neuronal Outgrowth/physiology , Neurons/cytology , Neurons/physiology , Spiral Ganglion/cytology , Spiral Ganglion/physiology , Young AdultABSTRACT
Concurrent hyperbaric oxygen therapy (HBOT) and intratympanic steroid application (ITS) are beneficial as salvage therapy for therapy-refractory sudden sensorineural hearing loss (SSNHL). The findings encourage further research on the treatment of noise-induced and idiopathic SSNHL with concurrent use of HBOT and ITS respecting also patients with long-term or therapy-refractory SSNHL.
ABSTRACT
BACKGROUND: Hyperbaric oxygen (HBO) seems to intensify the effect of ionising radiation. We investigated whether HBO combined with irradiation decreases the capability of U251 glioblastoma cells for relapse and metastasis. MATERIALS AND METHODS: Cells were treated with O2 at 1.3 bar and then irradiated with 2 Gy photons. Clonogenic survival was tested with colony formation. Motility is an important feature of metastasis and was measured with time-lapse videography. RESULTS: The clonogenic survival diminished by 22% through HBO, by 49% through irradiation, and by 70% through the combination of both. The accumulated distance travelled by cells fell by 3% with HBO, rose by 17% with irradiation, but was reduced by 11% with their combination. The respective values for the Euclidean distance travelled were +8%, +47% and -14%. Compared to normoxic irradiation, additional HBO lowered travel by 41%. CONCLUSION: HBO strengthens the effect of irradiation on clonogenic survival and reverses radiation-induced increase in the mobility of cells.
