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https://www.readbyqxmd.com/read/28608552/a-perspective-on-stem-cell-therapy-for-ear-disorders
#1
Rahul Mittal, Hyunseo D Jung, Jeenu Mittal, Adrien A Eshraghi
The use of stem cells in cell-based therapy is an emerging concept for the treatment of ear disorders. Tympanic membrane perforation (TMP) and inner ear disorders are some of the most commonly presented otologic disorders that can benefit from advances in cell-based therapy. Studies have already demonstrated that stem cell-based therapy can potentially be an effective treatment modality for acute and chronic TMP. Recent studies have also shown promise in application of cell-based approach to treat inner ear dysfunction...
June 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28571616/advances-in-translational-inner-ear-stem-cell-research
#2
REVIEW
Athanasia Warnecke, Adam J Mellott, Ariane Römer, Thomas Lenarz, Hinrich Staecker
Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types...
May 25, 2017: Hearing Research
https://www.readbyqxmd.com/read/28542481/effect-of-hyperbaric-oxygen-on-bdnf-release-and-neuroprotection-investigations-with-human-mesenchymal-stem-cells-and-genetically-modified-nih3t3-fibroblasts-as-putative-cell-therapeutics
#3
Jennifer Schulze, Odett Kaiser, Gerrit Paasche, Hans Lamm, Andreas Pich, Andrea Hoffmann, Thomas Lenarz, Athanasia Warnecke
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...
2017: PloS One
https://www.readbyqxmd.com/read/28532627/regenerative-medicine-in-hearing-recovery
#4
REVIEW
Edi Simoni, Giulia Orsini, Milvia Chicca, Simone Bettini, Valeria Franceschini, Alessandro Martini, Laura Astolfi
Hearing loss, or deafness, affects 360 million people worldwide of which about 32 million are children. Deafness is irreversible when it involves sensory hair cell death because the regenerative ability of these cells is lost in mammals after embryo development. The therapeutic strategies for deafness include hearing aids and/or implantable devices. However, not all patients are eligible or truly benefit from these medical devices. Regenerative medicine based on stem cell application could play a role in both improvement of extant medical devices and in vivo recovery of auditory function by regeneration of inner ear cells and neurons...
May 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28499298/-cochlear-implant-state-of-the-art
#5
Thomas Lenarz
Cochlear implants are the treatment of choice for the auditory rehabilitation of patients with sensory deafness. They restore the missing function of inner hair cells by transforming the acoustic signal into electrical stimuli for activation of auditory nerve fibers. Due to the very fast technology development cochlear implants provide open-set speech understanding in the majority of patients including the use of the telephone. Children can achieve a near to normal speech and language development provided their deafness is detected early after onset and implantation is performed quickly thereafter...
April 2017: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/28492243/identification-of-mouse-cochlear-progenitors-that-develop-hair-and-supporting-cells-in-the-organ-of-corti
#6
Jinshu Xu, Hiroo Ueno, Chelsea Y Xu, Binglai Chen, Irving L Weissman, Pin-Xian Xu
The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28459451/generation-of-inner-ear-organoids-containing-functional-hair-cells-from-human-pluripotent-stem-cells
#7
Karl R Koehler, Jing Nie, Emma Longworth-Mills, Xiao-Ping Liu, Jiyoon Lee, Jeffrey R Holt, Eri Hashino
The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate...
June 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28443600/retroauricular-approach-for-targeted-cochlear-therapy-experiments-in-wistar-albino-rats
#8
Selçuk Mülazımoğlu, Emre Ocak, Gülşah Kaygusuz, Mustafa Kürşat Gökcan
BACKGROUND: As the idea of stem cell technology in the treatment of sensorial hearing loss has emerged over the past decades, the need for in vivo models for related experiments has become explicit. One of the most common experimental models for inner ear stem cell delivery experiments is the Wistar albino rat. AIMS: To investigate the surgical anatomy of the temporal bone of the Wistar albino rat with respect to the dissection steps, operative techniques and potential pitfalls of surgery...
May 5, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28414155/recent-advances-in-cochlear-hair-cell-regeneration-a-promising-opportunity-for-the-treatment-of-age-related-hearing-loss
#9
REVIEW
Miren Revuelta, Francisco Santaolalla, Olatz Arteaga, Antonia Alvarez, Ana Sánchez-Del-Rey, Enrique Hilario
The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing...
July 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28393066/signaling-and-transcription-factors-during-inner-ear-development-the-generation-of-hair-cells-and-otic-neurons
#10
Héctor Gálvez, Gina Abelló, Fernando Giraldez
Integration between cell signals and bHLH transcription factors plays a prominent role during the development of hair cells of the inner ear. Hair cells are the sensory receptors of the inner ear, responsible for the mechano-transduction of sound waves into electrical signals. They derive from multipotent progenitors that reside in the otic placode. Progenitor commitment is the result of cell signaling from the surrounding tissues that result in the restricted expression of SoxB1 transcription factors, Sox2 and Sox3...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28361311/directed-differentiation-of-mouse-embryonic-stem-cells-into-inner-ear-sensory-epithelia-in-3d-culture
#11
Jing Nie, Karl R Koehler, Eri Hashino
The inner ear sensory epithelium harbors mechanosensory hair cells responsible for detecting sound and maintaining balance. This protocol describes a three-dimensional (3D) culture system that efficiently generates inner ear sensory epithelia from aggregates of mouse embryonic stem (mES) cells. By mimicking the activations and repressions of key signaling pathways during in vivo inner ear development, mES cell aggregates are sequentially treated with recombinant proteins and small molecule inhibitors for activating or inhibiting the Bmp, TGFβ, Fgf, and Wnt signaling pathways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28359931/transplanting-mouse-induced-pluripotent-stem-cells-into-mouse-otocysts-in-vivo
#12
Hiroki Takeda, Ryosei Minoda, Toru Miwa, Takao Yamada, Momoko Ise
The otocyst is an attractive target for studying treatment strategies for genetic hearing loss and for understanding inner ear development. We have previously reported that trans-uterine supplemental gene therapy in vivo into the otocysts of mice, which had a loss of function mutation in a causative gene of deafness, was able to prevent putative hearing loss. We herein set out to clarify the feasibility of allogenic cell transplantation into the mouse otocysts in vivo. We transplanted naive mouse-derived induced pluripotent stem cells (miPSCs) into the otocysts of wild type mice or connexin (Cx) 30 deficient mice, at embryonic day 11...
March 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28186679/directed-differentiation-of-human-embryonic-stem-cells-toward-placode-derived-spiral-ganglion-like-sensory-neurons
#13
Akihiro J Matsuoka, Zachery D Morrissey, Chaoying Zhang, Kazuaki Homma, Abdelhak Belmadani, Charles A Miller, Duncan M Chadly, Shun Kobayashi, Alexandra N Edelbrock, Miho Tanaka-Matakatsu, Donna S Whitlon, Ljuba Lyass, Tammy L McGuire, Samuel I Stupp, John A Kessler
The ability to generate spiral ganglion neurons (SGNs) from stem cells is a necessary prerequisite for development of cell-replacement therapies for sensorineural hearing loss. We present a protocol that directs human embryonic stem cells (hESCs) toward a purified population of otic neuronal progenitors (ONPs) and SGN-like cells. Between 82% and 95% of these cells express SGN molecular markers, they preferentially extend neurites to the cochlear nucleus rather than nonauditory nuclei, and they generate action potentials...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28025992/mir-124-promotes-the-neuronal-differentiation-of-mouse-inner-ear-neural-stem-cells
#14
Di Jiang, Jintao Du, Xuemei Zhang, Wei Zhou, Lin Zong, Chang Dong, Kaitian Chen, Yu Chen, Xihui Chen, Hongyan Jiang
MicroRNAs (miRNAs or miRs) act as key regulators in neuronal development, synaptic morphogenesis and plasticity. However, their role in the neuronal differentiation of inner ear neural stem cells (NSCs) remains unclear. In this study, 6 miRNAs were selected and their expression patterns during the neuronal differentiation of inner ear NSCs were examined by RT-qPCR. We demonstrated that the culture of spiral ganglion stem cells present in the inner ears of newborn mice gave rise to neurons in vitro. The expression patterns of miR‑124, miR‑132, miR‑134, miR‑20a, miR‑17-5p and miR‑30a-5p were examined during a 14-day neuronal differentiation period...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27966334/study-of-mouse-induced-pluripotent-stem-cell-transplantation-intowistar-albino-rat-cochleae-after-hair-cell-damage
#15
Mustafa Kürşat Gökcan, Selçuk Mülazimoğlu, Emre Ocak, Pınar Can, Murat Çalışkan, Ömer Beşaltı, Serpil Dizbay Sak, Gülşah Kaygusuz
BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach...
November 17, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27933352/intracochlear-drug-delivery-in%C3%A2-combination-with-cochlear-implants-current-aspects
#16
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
January 2017: HNO
https://www.readbyqxmd.com/read/27761977/concomitant-differentiation-of-a-population-of-mouse-embryonic-stem-cells-into-neuron-like-cells-and-schwann-cell-like-cells-in-a-slow-flow-microfluidic-device
#17
Poornapriya Ramamurthy, Joshua B White, Joong Yull Park, Richard I Hume, Fumi Ebisu, Flor Mendez, Shuichi Takayama, Kate F Barald
BACKGROUND: To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining spiral ganglion neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived "neurons" could potentially substitute for lost or damaged SGN...
January 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27757480/-intracochlear-drug-delivery-in-combination-with-cochlear-implants-current-aspects
#18
REVIEW
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (intratympanic injection); intracochlear administration, particularly for gene and stem cell therapy; as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
November 2016: HNO
https://www.readbyqxmd.com/read/27755610/bmi1-loss-in-the-organ-of-corti-results-in-p16ink4a-upregulation-and-reduced-cell-proliferation-of-otic-progenitors-in-vitro
#19
Mohamed Bassiouni, Aurélie Dos Santos, Hasan X Avci, Hubert Löwenheim, Marcus Müller
The mature mammalian organ of Corti does not regenerate spontaneously after injury, mainly due to the absence of cell proliferation and the depletion of otic progenitors with age. The polycomb gene B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) promotes proliferation and cell cycle progression in several stem cell populations. The cell cycle inhibitor p16ink4a has been previously identified as a downstream target of Bmi1. In this study, we show that Bmi1 is expressed in the developing inner ear. In the organ of Corti, Bmi1 expression is temporally regulated during embryonic and postnatal development...
2016: PloS One
https://www.readbyqxmd.com/read/27709784/morin-hydrate-promotes-inner-ear-neural-stem-cell-survival-and-differentiation-and-protects-cochlea-against-neuronal-hearing-loss
#20
Qiang He, Zhanwei Jia, Ying Zhang, Xiumin Ren
We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network...
March 2017: Journal of Cellular and Molecular Medicine
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