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https://www.readbyqxmd.com/read/28414155/recent-advances-in-cochlear-hair-cell-regeneration-a-promising-opportunity-for-the-treatment-of-age-related-hearing-loss
#1
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...
April 13, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27607106/modulation-of-wnt-signaling-enhances-inner-ear-organoid-development-in-3d-culture
#13
Rachel E DeJonge, Xiao-Ping Liu, Christopher R Deig, Stefan Heller, Karl R Koehler, Eri Hashino
Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles-a process that was previously self-organized by unknown mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27600399/contributions-of-mouse-and-human-hematopoietic-cells-to-remodeling-of-the-adult-auditory-nerve-after-neuron-loss
#14
Hainan Lang, Eishi Nishimoto, Yazhi Xing, LaShardai N Brown, Kenyaria V Noble, Jeremy L Barth, Amanda C LaRue, Kiyoshi Ando, Bradley A Schulte
The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier. This procedure also resulted in the upregulation of genes associated with hematopoietic cell homing and differentiation, and provided an environment conducive to the tissue engraftment of circulating stem/progenitor cells into the AN...
November 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27568193/the-unique-electrical-properties-in-an-extracellular-fluid-of-the-mammalian-cochlea-their-functional-roles-homeostatic-processes-and-pathological-significance
#15
REVIEW
Fumiaki Nin, Takamasa Yoshida, Seishiro Sawamura, Genki Ogata, Takeru Ota, Taiga Higuchi, Shingo Murakami, Katsumi Doi, Yoshihisa Kurachi, Hiroshi Hibino
The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K(+)] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K(+) to enter sensory hair cells and excite them. The positive EP accelerates this K(+) influx, thereby sensitizing hearing. K(+) exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K(+) to the endolymph...
October 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27536218/epigenetic-dna-demethylation-causes-inner-ear-stem-cell-differentiation-into-hair-cell-like-cells
#16
Yang Zhou, Zhengqing Hu
The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27474107/evaluation-of-nestin-expression-in-the-developing-and-adult-mouse-inner-ear
#17
Cynthia L Chow, Parul Trivedi, Madeline P Pyle, Jacob T Matulle, Robert Fettiplace, Samuel P Gubbels
Adult stem cells are undifferentiated cells with the capacity to proliferate and form mature tissue-specific cell types. Nestin is an intermediate filament protein used to identify cells with stem cell characteristics. Its expression has been observed in a population of cells in developing and adult cochleae. In vitro studies using rodent cochlear tissue have documented the potential of nestin-expressing cells to proliferate and form hair and supporting cells. In this study, nestin coupled to green fluorescent protein (GFP) transgenic mice were used to provide a more complete characterization of the spatial and temporal expression of nestin in the inner ear, from organogenesis to adulthood...
October 1, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27402757/single-cell-analysis-delineates-a-trajectory-toward-the-human-early-otic-lineage
#18
Megan Ealy, Daniel C Ellwanger, Nina Kosaric, Andres P Stapper, Stefan Heller
Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage...
July 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27215798/functional-development-of-mechanosensitive-hair-cells-in-stem-cell-derived-organoids-parallels-native-vestibular-hair-cells
#19
Xiao-Ping Liu, Karl R Koehler, Andrew M Mikosz, Eri Hashino, Jeffrey R Holt
Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs...
May 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27108805/planar-cell-polarity-pcp-proteins-and-spermatogenesis
#20
REVIEW
Haiqi Chen, C Yan Cheng
In adult mammalian testes, spermatogenesis is comprised of several discrete cellular events that work in tandem to support the transformation and differentiation of diploid spermatogonia to haploid spermatids in the seminiferous epithelium during the seminiferous epithelial cycle. These include: self-renewal of spermatogonial stem cells via mitosis and their transformation into differentiated spermatogonia, meiosis I/II, spermiogenesis and the release of sperms at spermiation. Studies have shown that these cellular events are under precise and coordinated controls of multiple proteins and signaling pathways...
November 2016: Seminars in Cell & Developmental Biology
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