Copyright © 2014 Yu Jiao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is... more
Copyright © 2014 Yu Jiao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation.Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of
The incidence of otitis media in children between the age of 2 and 6 years is well documented. Repeated attacks may cause acute and chronic perforations. The surgical treatment for repairing chronic perforation is quite uncomfortable for... more
The incidence of otitis media in children between the age of 2 and 6 years is well documented. Repeated attacks may cause acute and chronic perforations. The surgical treatment for repairing chronic perforation is quite uncomfortable for the patients of this age group because of the invasiveness of this treatment. The aim of this study was to determine the long-term influence of embryonic stem cells on acute perforations and the effect of gelatin as a vehicle for applied stem cells. The possibility of teratogenic effects of the stem cells was also observed. Bilateral laser myringotomy was performed in 17 adult Sprague-Dawley rats, divided into two groups. Gelatin, a substance suitable as vehicle for bioactive material was used bilaterally around the perforation in group A, to serve as a scaffold for repairing tissue. The stem cells were used in the right tympanic membrane perforation leaving the left tympanic membrane as a control. The animals in group B received the same treatment ...
Research Interests: Wound Healing, Morphology, Treatment Outcome, Stem Cell, Medicine, and 13 moreStem Cell Transplantation, Female, Animals, Follow-up studies, Clinical Sciences, Rats, Time Factors, Perforation, Rat, Otitis Media, Tympanic Membrane Perforation, Tympanic Membrane, and Paediatrics and reproductive medicine
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Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional... more
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host. One option for in vitro studies is to examine the integration of exogenous stem cells into an existing active neural network in ex vivo organotypic cultures. Organotypic cultures leave the structural integrity essentially intact while still allowing the microenvironment to be carefully controlled. This allows detailed studies over time of cellular responses and cell-cell interactions, which are not readily performed in vivo. This unit describes procedures for using orga...
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Progress in techniques and strategies for tissue engineering has increased our interest in allografting and xenografting in various organ systems. Previous work has shown that peripherally implanted fetal dorsal root ganglion neurons... more
Progress in techniques and strategies for tissue engineering has increased our interest in allografting and xenografting in various organ systems. Previous work has shown that peripherally implanted fetal dorsal root ganglion neurons (DRGs) can grow axons across the boundary between the central and peripheral nervous system in the dorsal root and make functional connections within the spinal cord. We have extended this experimental paradigm to the auditory system and successfully implanted fetal DRG neurons into the normal and deafened cochlea, adjacent to deafferented auditory spiral ganglion neurons. These findings demonstrate the feasibility of using fetal sensory cells in a new strategy to repair or replace the auditory nerve. Further studies will show whether the surviving DRGs can restore a functional conduit from the cochlea to the brainstem. If so, implanting neuronal tissue close to the auditory nerve could be used to regain auditory function in e.g. profoundly deaf patients.
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Tympanic membrane perforations may cause hearing impairment and otorhea. It is a common indication for ear surgery. The aim of the study was to test whether stem cells may enhance the healing of fresh tympanic membrane perforations. In a... more
Tympanic membrane perforations may cause hearing impairment and otorhea. It is a common indication for ear surgery. The aim of the study was to test whether stem cells may enhance the healing of fresh tympanic membrane perforations. In a first assay, the status of the tympanic membrane at 5 days after myringotomy was tested in five Mongolian gerbils that were treated on one side with embryonic stem cells and on the other side with control substance. In a second assay, nine gerbils were treated in the same way, except that fluorescent-labeled embryonic stem cells were used. The integration of the stem cells into the surface layer of the healing tympanic membrane was assessed with fluorescence microscopy, as well as the differentiation of these cells. In the first assay, all perforations in the treated ears were closed, whereas only two of the untreated ears were closed. The strength of the healed perforation was greater in the stem cell treated tympanic membranes (mean rupture pressu...
Research Interests: Pathology, Stem Cells, Fluorescence Microscopy, Treatment, Human embryonic stem cell, and 15 moreStem Cell, Stem Cell Transplantation, Animals, Embryonic Stem Cell, Healing, Pediatric, Clinical Sciences, Tympanum, Time Factors, Perforation, Hearing Impaired, Tympanic Membrane Perforation, Tympanic Membrane, Gerbillinae, and Paediatrics and reproductive medicine
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Research Interests: Psychology, Cell Culture, Cell therapy, Female, Animals, and 15 moreFunctional Assessment, Clinical Sciences, Functional integration, Neurite, Degeneration, Olfactory Bulb, Nervous System, Experimental Neurology, Cell Survival, Neurosciences, Neurite Outgrowth, Brain stem, Cochlear Nucleus, coculture techniques, and axon growth
Research Interests: Technology, Transgenic Mice, Biological Sciences, Cell Differentiation, Pregnancy, and 13 moreMice, Female, Animals, Embryonic Stem Cell, Embryonic Stem Cells, Rats, Auditory Cortex, Cell Survival, DNA binding proteins, Brain stem, High mobility group proteins, coculture techniques, and Medical and Health Sciences
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Research Interests: Cognitive Science, Embryo, Clinical Practice, Brain, Mice, and 15 moreAnimals, Cell Transplantation, Inner Ear, Mantle Transition Zone, Hearing Impaired, Fluorescent Protein, Nervous System, Neural Stem Cells, ABR, Auditory Brainstem Response, Auditory Nerve, GFP, Neurosciences, Brain stem, and Cochlear Nucleus
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Three different donor tissues were tested for their capacity to survive, integrate and differentiate in the adult inner ear. Surviving embryonic dorsal root ganglion cells were found within the spiral ganglion neuron region and along the... more
Three different donor tissues were tested for their capacity to survive, integrate and differentiate in the adult inner ear. Surviving embryonic dorsal root ganglion cells were found within the spiral ganglion neuron region and along the auditory nerve fibers. In the presence of exogenous nerve growth factor (NGF), the dorsal root ganglion cells formed extensive growth of neurites that seemed to contact the host neurons. Adult neural stem cells survived relative poorly in the inner ear whereas embryonic stem cells showed a somewhat greater capacity for survival and integration. Overall, the survival rate of implanted tissue was quite low in the cochlea. It is concluded that an inner ear cell therapy approach based on the implantation of exogenous cells will require that important survival factors are identified and supplied. In addition, it is possible that the physical properties of the cochlea, e.g., fluid-filled compartments and very limited space for cell proliferation, are unfavorable, at least in the normal cochlea.
Research Interests: Treatment, Adult Stem Cells, Stem Cell, Stem Cell Transplantation, Embryo, and 20 moreBiological Sciences, Neural stem cell, Cell therapy, Cell Differentiation, Mice, Animals, Embryonic Stem Cell, Embryonic Stem Cells, Neurons, Inner Ear, Rats, Survival Rate, Neural, Cell Proliferation, Nerve Growth Factor, Auditory Nerve, Cochlea, Cell Survival, Physical Properties, and Spiral Ganglion
Patients undergoing temporal bone surgery or subjects working with vibrating tools may develop vibration-induced hearing loss (VHL). The aim of this study was to characterize the effects of pretreatment with N-acetylcysteine (NAC) or the... more
Patients undergoing temporal bone surgery or subjects working with vibrating tools may develop vibration-induced hearing loss (VHL). The aim of this study was to characterize the effects of pretreatment with N-acetylcysteine (NAC) or the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), on VHL in an animal model. Trauma to the cochlea was created with a vibrating probe placed on the bone of the external ear canal. BDNF and CNTF(Ax1) were delivered into the cochlea with mini-osmotic pumps. NAC was delivered into the cochlea by round window membrane (RWM) injection, by RWM permeation, or by oral administration. Hearing was evaluated with electrocochleography (ECoG). For control animals, vibration resulted in an average immediate threshold shift of 42 +/- 26 dB. NAC provided no protective benefit in animals subjected to VHL, regardless of the delivery method, with average threshold shifts varying from 38 to 56 dB across groups. NAC i...
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Three different donor tissues were tested for their capacity to survive, integrate and differentiate in the adult inner ear. Surviving embryonic dorsal root ganglion cells were found within the spiral ganglion neuron region and along the... more
Three different donor tissues were tested for their capacity to survive, integrate and differentiate in the adult inner ear. Surviving embryonic dorsal root ganglion cells were found within the spiral ganglion neuron region and along the auditory nerve fibers. In the presence of exogenous nerve growth factor (NGF), the dorsal root ganglion cells formed extensive growth of neurites that seemed to contact the host neurons. Adult neural stem cells survived relative poorly in the inner ear whereas embryonic stem cells showed a somewhat greater capacity for survival and integration. Overall, the survival rate of implanted tissue was quite low in the cochlea. It is concluded that an inner ear cell therapy approach based on the implantation of exogenous cells will require that important survival factors are identified and supplied. In addition, it is possible that the physical properties of the cochlea, e.g., fluid-filled compartments and very limited space for cell proliferation, are unfavorable, at least in the normal cochlea.
Research Interests: Treatment, Adult Stem Cells, Stem Cell, Stem Cell Transplantation, Embryo, and 20 moreBiological Sciences, Neural stem cell, Cell therapy, Cell Differentiation, Mice, Animals, Embryonic Stem Cell, Embryonic Stem Cells, Neurons, Inner Ear, Rats, Survival Rate, Neural, Cell Proliferation, Nerve Growth Factor, Auditory Nerve, Cochlea, Cell Survival, Physical Properties, and Spiral Ganglion
Cell replacement therapy in the inner ear will contribute to the functional recovery of hearing loss. Cell replacement therapy is a potentially powerful approach to replace degenerated or severely damaged spiral ganglion neurons. This... more
Cell replacement therapy in the inner ear will contribute to the functional recovery of hearing loss. Cell replacement therapy is a potentially powerful approach to replace degenerated or severely damaged spiral ganglion neurons. This study aimed at stimulating the neurite outgrowth of the implanted neurons and enhancing the potential therapeutic of inner ear cell implants. Chronic electrical stimulation (CES) and exogenous neurotrophic growth factor (NGF) were applied to 46 guinea pigs transplanted with embryonic dorsal root ganglion (DRG) neurons 4 days postdeafening. The animals were evaluated with the electrically evoked auditory brainstem responses (EABRs) at experimental Days 7, 11, 17, 24, and 31. The animals were euthanized at Day 31, and the inner ears were dissected for immunohistochemistry investigation. Implanted DRG cells, identified by enhanced green fluorescent protein fluorescence and a neuronal marker, were found close to Rosenthal canal in the adult inner ear for up to 4 weeks after transplantation. Extensive neurite projections clearly, greater than in nontreated animals, were observed to penetrate the bony modiolus and reach the spiral ganglion region in animals supplied with CES and/or NGF. There was, however, no significant difference in the thresholds of EABRs between DRG-transplanted animals supplied with CES and/or NGF and DRG-transplanted animals without CES or NGF supplement. The results suggest that CES and/or NGF can stimulate neurite outgrowth from implanted neurons, although based on EABR measurement, these interventions did not induce functional connections to the central auditory pathway. Additional time or novel approaches may enhance functional responsiveness of implanted cells in the adult cochlea.
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Research Interests: Neurobiology Of Disease, Cell Differentiation, Cochlear Implant, Female, Animals, and 15 moreMale, Hearing Loss, Neurons, Inner Ear, Nerve Regeneration, Clinical Sciences, Rats, Degeneration, Nervous System, Cell Proliferation, Nerve Growth Factor, Somatic Cell Count, Neurosciences, Neurite Outgrowth, and Spiral Ganglion
Research Interests: Psychology, Surgery, Treatment, Cochlear Implant, Mice, and 18 moreAnimals, Feasibility Studies, Auditory System, Hearing Loss, Neurons, Inner Ear, Green Fluorescent Protein, Feasibility, Clinical Sciences, Rats, Functional Recovery, Rat, Degeneration, Experimental Neurology, organ of Corti, Cell Survival, Neurosciences, and Postoperative Period
The regeneration of the auditory nerve remains a challenge in restoring hearing. An interesting approach would be to use a cell replacement therapy with the potential to establish connections from the inner ear to the central auditory... more
The regeneration of the auditory nerve remains a challenge in restoring hearing. An interesting approach would be to use a cell replacement therapy with the potential to establish connections from the inner ear to the central auditory system. This hypothesis was tested by xenografted (mouse to rat) implantation of embryonic dorsal root ganglion (DRG) neurons and embryonic stem (ES) cells along the auditory nerve in the adult host. DRG neurons were obtained at embryonic day 13-14 in transgenic animals expressing enhanced green fluorescence protein (EGFP). For embryonic stem cells, a tau-GFP ES cell line was used as a donor. The fibers of the auditory nerve in the adult rat were transected through the modiolus at the first cochlear turn, and the biological implants were transplanted into the transection. The transplanted DRG neurons and ES cells survived for a postoperative survival time ranging from 3 to 9 weeks, verified by EGFP/GFP fluorescence, and neurofilament or TUJ1 immunostaining. At 9 weeks following implantation, the implanted DRG neurons were found to have migrated along the auditory nerve in the internal meatus. At the same postoperative time, the ES cells had migrated into the brain stem close to the ventral cochlear nucleus. The results demonstrate not only the survival and migration of xenografted DRG neurons and stem cells along the adult auditory nerve but also the feasibility of a cell replacement therapy in the degenerated auditory system.
Research Interests: Cognitive Science, Stem Cells, Human Embryonic Stem Cells, Migration, Immunohistochemistry, and 22 moreStem Cell, Stem Cell Transplantation, Embryo, Brain, Animals, Embryonic Stem Cell, Transgenic Animals, Auditory System, Hearing Loss, Neurons, Inner Ear, Rats, Time Factors, Rat, Degeneration, Tubulin, Auditory Nerve, Cell Survival, Survival Time, Neurosciences, ES cell, and Brain stem
This technique enabled us to visualize the cochlea without causing damage. The mammalian inner ear is difficult to approach surgically. This is particularly true in the cases of the rat and mouse, which both have small cochleae. Rat and... more
This technique enabled us to visualize the cochlea without causing damage. The mammalian inner ear is difficult to approach surgically. This is particularly true in the cases of the rat and mouse, which both have small cochleae. Rat and mouse research is particularly important because their genomes are well characterized, and significantly similar to that of the human. The aim of the present study was to develop a method of accessing the rat cochlea without affecting its function. In the ventral approach, a small hole was made for access to the scala tympani. Cochlear function was assessed through auditory brainstem response (ABR) threshold measurements. The ventral approach enabled the direct visualization of the tympanic bulla. Thus, the tympanic bulla could be easily opened in a manner that was benign to cochlear function. There was no significant difference in ABR threshold before and after surgery.
Research Interests: Medicine, Female, Animals, Male, ENT, and 9 moreInner Ear, Clinical Sciences, Rats, Rat, Auditory Threshold, ABR, Cochlea, Brain stem, and Postoperative Complications
Important information about the basic reparative process of tympanic membrane (TM) healing is shown, which can be incorporated for further clinical understanding. This provides a basis for the exploration of stem cell treatment for TM... more
Important information about the basic reparative process of tympanic membrane (TM) healing is shown, which can be incorporated for further clinical understanding. This provides a basis for the exploration of stem cell treatment for TM perforations and holds promise for future improvements. This study aimed to analyse the healing of TM perforation by using stem cells and the stiffness of the membrane was tested in an acute and long-term study. Sprague-Dawley rats were used in a model of TM perforation. The perforation was performed with a laser system. Stem cells were applied and the healing time and morphological analysis were performed with light and transmission electron microscope. Stiffness was examined by moiré interferometry. The stiffness of the perforated and healed TM was restored after just 2 weeks. In the chronic perforation model, mesenchymal stem cells enhanced the healing.
Research Interests: Surgery, Sound, Treatment, Wound Healing, Treatment Outcome, and 15 moreTransmission Electron Microscopy, Stem Cell, Stem Cell Transplantation, Interferometry, Chronic Disease, Animals, Follow-up studies, ENT, Healing, Clinical Sciences, Tympanum, Rats, Perforation, Tympanic Membrane Perforation, and Tympanic Membrane
Hearing function lost by degeneration of inner ear spiral ganglion neurons (SGNs) in the auditory nervous system could potentially be compensated by cellular replacement using suitable donor cells. Donor cell-derived neuronal development... more
Hearing function lost by degeneration of inner ear spiral ganglion neurons (SGNs) in the auditory nervous system could potentially be compensated by cellular replacement using suitable donor cells. Donor cell-derived neuronal development with functional synaptic formation with auditory neurons of the cochlear nucleus (CN) in the brainstem is a prerequisite for a successful transplantation. Here a rat auditory brainstem explant culture system was used as a screening platform for donor cells. The explants were co-cultured with human neural precursor cells (HNPCs) to determine HNPCs developmental potential in the presence of environmental cues characteristic for the auditory brainstem region in vitro. We explored effects of pharmacological inhibition of GTPase Rho with its effector Rho-associated kinase (ROCK) and epidermal growth factor receptor (EGFR) signaling on the co-cultures. Pharmacological agents ROCK inhibitor Y27632 and EGFR blocker PD168393 were tested. Effect of the treatm...
Research Interests: Neuroscience, Psychology, ANOVA, Rock, PDL, and 8 moreNC, PBS, Moi, HBSS, MEF, CM, GFP, and Neurosciences
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional... more
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host. One option for in vitro studies is to examine the integration of exogenous stem cells into an existing active neuronal network in ex vivo organotypic cultures. Organotypic cultures leave the structural integrity essentially intact while still allowing the microenvironment to be carefully controlled. This allows detailed studies over time of cellular responses and cell-cell interactions, which are not readily performed in vivo. This unit describes procedures for using organotypic slice cultures as ex vivo model systems for studying neural stem cell and embryonic stem cell engraftment and communication with CNS host tissue.
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The aim of this study was to analyze the short-term viscoelastic and histologic properties of scarred rabbit vocal folds after injection of human mesenchymal stem cells (MSC) as well as the degree of MSC survival. Because MSCs are... more
The aim of this study was to analyze the short-term viscoelastic and histologic properties of scarred rabbit vocal folds after injection of human mesenchymal stem cells (MSC) as well as the degree of MSC survival. Because MSCs are antiinflammatory and regenerate mesenchymal tissues, can MSC injection reduce vocal fold scarring after injury? Twelve vocal folds from 10 New Zealand rabbits were scarred by a localized resection and injected with human MSC or saline. Eight vocal folds were left as controls. After 4 weeks, 10 larynges were stained for histology and evaluation of the lamina propria thickness. Collagen type I content was analyzed from six rabbits. MSC survival was analyzed by fluorescent in situ hybridization staining from three rabbits. Viscoelasticity for 10 vocal folds was analyzed in a parallel-plate rheometer. The rheometry on fresh-frozen samples showed decreased dynamic viscosity and lower elastic modulus (P<.01) in the scarred samples injected with MSC as compared with the untreated scarred group. Normal controls had lower dynamic viscosity and elastic modulus as compared with the scarred untreated and treated vocal folds (P<.01). Histologic analysis showed a higher content of collagen type 1 in the scarred samples as compared with the normal vocal folds and with the scarred folds treated with MSC. MSCs remained in all samples analyzed. The treated scarred vocal folds showed persistent MSC. Injection of scarred rabbit vocal folds with MSC rendered improved viscoelastic parameters and less signs of scarring expressed as collagen content in comparison to the untreated scarred vocal folds.
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Research Interests: Multidisciplinary, Hearing, Humans, Animals, Auditory System, and 14 moreCochlear Implants, Neurons, Inner Ear, Deafness, Degeneration, Guinea Pig, Peripheral Nerve, Auditory Brainstem Response, Auditory Nerve, Cell Survival, Cochlear Implantation, Ciliary Neurotrophic Factor, Functional Response, and Acoustic Stimulation
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Research Interests: Neuroscience, Psychology, Stem Cell, Embryo, In Vitro, and 29 moreCell Differentiation, Ir, Mice, Animals, Embryonic Stem Cell, Plant tissue Culture Techniques, Sensory Neuron, Embryonic Stem Cells, Hearing Loss, Cell Transplantation, Neurons, Differentiation, Inner Ear, Green Fluorescent Protein, Neuronal Differentiation, Rats, SYNAPSES, PBS, Fluorescent Protein, LIF, GDNF, HBSS, MEF, Sgn, Cell Survival, GFP, Neurosciences, Brain stem, and Cochlear Nucleus
Benefits of cochlear prostheses for the deaf are dependent on survival and excitability of the auditory nerve. Degeneration of deafferented auditory nerve fibers is prevented and excitability maintained by immediate replacement therapy... more
Benefits of cochlear prostheses for the deaf are dependent on survival and excitability of the auditory nerve. Degeneration of deafferented auditory nerve fibers is prevented and excitability maintained by immediate replacement therapy with exogenous neurotrophic factors, in vivo. It is important to know whether such interventions are effective after a delay following deafness, typical for the human situation. This study evaluated the efficacy of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor axokine-1 analogue (CNTF Ax1) application, 2 or 6 weeks postdeafening, in preventing further degeneration and a decrease in excitability. Guinea pigs were deafened and implanted with intracochlear stimulating electrodes, a scala tympani cannula-osmotic pump system, and auditory brainstem response (ABR) recording electrodes. Subjects received BDNF + CNTF Ax1 or artificial perilymph (AP) treatment for 27 days, beginning at 2 or 6 weeks following deafening. Electrical (E) ABR thresholds increased following deafening. After 1 week, in the 2-weeks-delayed neurotrophic factor treatment group, EABR thresholds decreased relative to AP controls, which were statistically significant at 2 weeks. In the 6-week delay group, a tendency to enhanced EABR sensitivity began at 2 weeks of treatment and increased thereafter, with a significant difference between neurotrophic factor- and AP-treated groups across the treatment period. A clear, statistically significant, enhanced survival of spiral ganglion cells was seen in both neurotrophic factor treatment groups relative to AP controls. These findings demonstrate that BDNF + CNTF Ax1 can act to delay or possibly even reverse degenerative and, likely apoptotic, processes well after they have been activated. These survival factors can rescue cells from death and enhance electrical excitability, even during the period of degeneration and cell loss when the spiral ganglion cell population is reduced by >50% (6 weeks). It is noteworthy that this same degree of ganglion cell loss, secondary to receptor damage, is typically observed after a period equivalent to some years of deafness in humans.
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Research Interests: Psychology, Stem Cells, Functional Connectivity, Neural stem cell, Sensorineural Hearing Loss, and 21 moreCochlear Implant, Mice, Animals, Spinal Cord, Embryonic Stem Cell, Central Nervous System, Embryonic Stem Cells, Cell Transplantation, Neurons, Inner Ear, Clinical Sciences, Dorsal root ganglia, Rats, Time Factors, Guinea Pig, Experimental Neurology, Transgenic Mouse Technology, Neurosciences, Clinical Application, ES cell, and Brain stem
Immature dorsal root ganglion (DRG) neurons have previously been shown to survive implantation to the cavity of extirpated adult native DRG, send axons via the dorsal root into the host spinal cord and make functional sypnatic... more
Immature dorsal root ganglion (DRG) neurons have previously been shown to survive implantation to the cavity of extirpated adult native DRG, send axons via the dorsal root into the host spinal cord and make functional sypnatic connections. Regeneration or replacement of the auditory nerve would provide a major intervention in the clinical treatment of severe hearing impairment. In this study we have exploited the potential of fetal DRG neurons to survive allografting into the cochlea of adult guinea pigs. In some animals implantation of fetal DRGs was combined with infusion of neurotropic substances into the cochlea. Survival of the implanted DRG neurons was found in the majority of grafted animals. Treatment with neurotrophic factors significantly increased the number of surviving implanted DRG neurons. However, even in the absence of neurotrophic substances survival of DRG neurons was found in a majority of the animals, indicating the presence of endogenous growth promoting factors within the cochlea and/or an intrinsic capacity of fetal DRG neurons themselves to survive in this heterotropic location.