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https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#1
Alex M Rohacek, Thomas W Bebee, Richard K Tilton, Caleb M Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A Germiller, Ian D Krantz, Russ P Carstens, Douglas J Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1(-/-) mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28864419/epiphycan-is-specifically-expressed-in-cochlear-supporting-cells-and-is-necessary-for-normal-hearing
#2
Yukiko Hanada, Yukiko Nakamura, Yusuke Ishida, Yasumitsu Takimoto, Manabu Taniguchi, Yoshiyuki Ozono, Yoshihisa Koyama, Tetsuo Morihana, Takao Imai, Yumi Ota, Takashi Sato, Hidenori Inohara, Shoichi Shimada
The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28814279/musashi-1-is-the-candidate-of-the-regulator-of-hair-cell-progenitors-during-inner-ear-regeneration
#3
Takahiro Wakasaki, Hiroaki Niiro, Siamak Jabbarzadeh-Tabrizi, Mitsuru Ohashi, Takashi Kimitsuki, Takashi Nakagawa, Shizuo Komune, Koichi Akashi
BACKGROUND: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells...
August 16, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28689068/efficient-induction-of-inner-ear-hair-cell-like-cells-from-mouse-es-cells-using-combination-of-math1-transfection-and-conditioned-medium-from-st2-stromal-cells
#4
Yukiteru Ouji, Masaharu Sakagami, Hiroko Omori, Shinji Higashiyama, Norikazu Kawai, Tadashi Kitahara, Akio Wanaka, Masahide Yoshikawa
We sought to establish a more efficient technique for induction of inner ear hair cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a combination of two previously reported methods; ST2 stromal cell-conditioned medium, known to be favorable for HC-like cell induction (HIST2 method), and ES cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying Tet-inducible Math1 were cultured for 14days with doxycycline in conditioned medium from cultures of ST2 stromal cells following formation of 4-day embryoid bodies (EBs)...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28686713/transcriptome-wide-comparison-of-the-impact-of-atoh1-and-mir-183-family-on-pluripotent-stem-cells-and-multipotent-otic-progenitor-cells
#5
COMPARATIVE STUDY
Michael Ebeid, Prashanth Sripal, Jason Pecka, Kirk W Beisel, Kelvin Kwan, Garrett A Soukup
Over 5% of the global population suffers from disabling hearing loss caused by multiple factors including aging, noise exposure, genetic predisposition, or use of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after HC loss is the limited ability of mammalian auditory HCs to spontaneously regenerate. Understanding the molecular mechanisms orchestrating HC development is expected to facilitate cell replacement therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28662075/microarray-analyses-of-otospheres-derived-from-the-cochlea-in-the-inner-ear-identify-putative-transcription-factors-that-regulate-the-characteristics-of-otospheres
#6
Takehiro Iki, Michihiro Tanaka, Shin-Ichiro Kitajiri, Tomoko Kita, Yuri Kawasaki, Akifumi Mizukoshi, Wataru Fujibuchi, Takayuki Nakagawa, Tatsutoshi Nakahata, Juichi Ito, Koichi Omori, Megumu K Saito
Various tissues possess tissue-specific stem/progenitor cells, including the inner ears. Stem/progenitor cells of the inner ear can be isolated as so-called otospheres from differentiated cells using a sphere forming assay. Although recent studies have demonstrated the characteristics of otospheres to some extent, most of the features of these cells are unknown. In this report, we describe the findings of transcriptome analyses with a cDNA microarray of otospheres derived from the cochleae of the inner ears of neonatal mice in order to clarify the gene expression profile of otic stem/progenitor cells...
2017: PloS One
https://www.readbyqxmd.com/read/28608552/a-perspective-on-stem-cell-therapy-for-ear-disorders
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
April 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28186679/directed-differentiation-of-human-embryonic-stem-cells-toward-placode-derived-spiral-ganglion-like-sensory-neurons
#19
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
#20
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
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