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https://www.readbyqxmd.com/read/29740017/atoh1-rfx1-rfx3-transcription-factors-facilitate-the-differentiation-and-characterisation-of-inner-ear-hair-cell-like-cells-from-patient-specific-induced-pluripotent-stem-cells-harbouring-a8344g-mutation-of-mitochondrial-dna
#1
Yen-Chun Chen, Chia-Ling Tsai, Yau-Huei Wei, Yu-Ting Wu, Wei-Ting Hsu, Hung-Ching Lin, Yi-Chao Hsu
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles...
April 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29570699/microrna-194-regulates-the-development-and-differentiation-of-sensory-patches-and-statoacoustic-ganglion-of-inner-ear-by-fgf4
#2
Hui Cao, Jianbo Shi, Jintao Du, Kaitian Chen, Chang Dong, Di Jiang, Hongyan Jiang
BACKGROUND MicroRNA 194 is involved in the differentiation of various types of cells, such as adipose derived stem cells, human embryonic stem cells, and bone marrow mesenchymal stem cells. Previously, we found that miR-194 was highly expressed in the inner ear sensory patch and neurons in mice embryos. However, the role of miR-194 in the development of the inner ear and its underlying mechanism have not been elucidated yet. MATERIAL AND METHODS The expression level of miR-194 has been altered by using antisense morpholino oligonucleotides (MO) and synthesized miRNAs in zebrafish...
March 23, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29491041/cerebral-organoids-ethical-issues-and-consciousness-assessment
#3
Andrea Lavazza, Marcello Massimini
Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue...
February 28, 2018: Journal of Medical Ethics
https://www.readbyqxmd.com/read/29487598/macrophages-in-the-human-cochlea-saviors-or-predators-a-study-using-super-resolution-immunohistochemistry
#4
Wei Liu, Matyas Molnar, Carolyn Garnham, Heval Benav, Helge Rask-Andersen
The human inner ear, which is segregated by a blood/labyrinth barrier, contains resident macrophages [CD163, ionized calcium-binding adaptor molecule 1 (IBA1)-, and CD68-positive cells] within the connective tissue, neurons, and supporting cells. In the lateral wall of the cochlea, these cells frequently lie close to blood vessels as perivascular macrophages. Macrophages are also shown to be recruited from blood-borne monocytes to damaged and dying hair cells induced by noise, ototoxic drugs, aging, and diphtheria toxin-induced hair cell degeneration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29477628/corrigendum-to-barhl1-is-required-for-the-differentiation-of-inner-ear-hair-cell-like-cells-from-mouse-embryonic-stem-cells-int-j-biochem-cell-biol-96-2018-79-89
#5
Chao Zhong, Zhenhuang Chen, Xiaocui Luo, Cuicui Wang, Hui Jiang, Jianzhong Shao, Minxin Guan, Liquan Huang, Xiao Huang, Jinfu Wang
No abstract text is available yet for this article.
April 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29450596/-strategies-for-a-regenerative-therapy-of-hearing-loss-german-version
#6
REVIEW
M Diensthuber, T Stöver
Despite impressive technical progress in the field of conventional hearing aids and implantable hearing systems, the hopes for the treatment of inner ear diseases such as hearing loss and tinnitus have become increasingly directed toward regenerative therapeutic approaches. This review discusses the currently most promising strategies for hair cell regeneration in the inner ear to treat hearing loss, including stem cell-based, gene transfer-based, and pharmacological interventions. Furthermore, previous milestones and ground-breaking work in this scientific field are identified...
March 2018: HNO
https://www.readbyqxmd.com/read/29413750/barhl1-is-required-for-the-differentiation-of-inner-ear-hair-cell-like-cells-from-mouse-embryonic-stem-cells
#7
Chao Zhong, Zhenhuang Chen, Xiaocui Luo, Cuicui Wang, Hui Jiang, Jianzhong Shao, Minxin Guan, Liquan Huang, Xiao Huang, Jinfu Wang
Inner ear hair cells are mechanoreceptors responsible for hearing. Pathogenic defects of hair cell-specific genes are one of the major causes of deafness. The BarH class homeobox gene Barhl1 is a deafness gene expressed in developing hair cells, yet the role of Barhl1 during hair cell development remains poorly understood. In the present study, we first established an in vitro differentiation system to efficiently obtain mouse embryonic stem cell (mESC)-derived hair cell-like cells. Subsequently, a mESC line carrying a targeted disruption of Barhl1 was generated using CRISPR/Cas9 technology and subjected to the established in vitro hair cell differentiation protocol...
March 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29386634/engraftment-of-human-pluripotent-stem-cell-derived-progenitors-in-the-inner-ear-of-prenatal-mice
#8
Hiroki Takeda, Makoto Hosoya, Masato Fujioka, Chika Saegusa, Tsubasa Saeki, Toru Miwa, Hideyuki Okano, Ryosei Minoda
There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29364256/a-protocol-for-decellularizing-mouse-cochleae-for-inner-ear-tissue-engineering
#9
Christopher A Neal, Jennifer G Nelson-Brantley, Michael S Detamore, Hinrich Staecker, Adam J Mellott
In mammals, mechanosensory hair cells that facilitate hearing lack the ability to regenerate, which has limited treatments for hearing loss. Current regenerative medicine strategies have focused on transplanting stem cells or genetic manipulation of surrounding support cells in the inner ear to encourage replacement of damaged stem cells to correct hearing loss. Yet, the extracellular matrix (ECM) may play a vital role in inducing and maintaining function of hair cells, and has not been well investigated. Using the cochlear ECM as a scaffold to grow adult stem cells may provide unique insights into how the composition and architecture of the extracellular environment aids cells in sustaining hearing function...
January 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29336130/comparison-of-three-types-of-mesenchymal-stem-cells-bone-marrow-adipose-tissue-and-umbilical-cord-derived-as-potential-sources-for-inner-ear-regeneration
#10
REVIEW
Mohammad-Reza Mahmoudian-Sani, Ameneh Mehri-Ghahfarrokhi, Morteza Hashemzadeh-Chaleshtori, Masoud Saidijam, Mohammad-Saeid Jami
In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy...
December 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/29327735/acquired-sensorineural-hearing-loss-in-children-current-research-and-therapeutic-perspectives
#11
M Ralli, R Rolesi, R Anzivino, R Turchetta, A R Fetoni
The knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic...
December 2017: Acta Otorhinolaryngologica Italica
https://www.readbyqxmd.com/read/29318324/strategies-for-a-regenerative-therapy-of-hearing-loss
#12
REVIEW
M Diensthuber, T Stöver
Despite impressive technical progress in the field of conventional hearing aids and implantable hearing systems, the hopes for the treatment of inner ear diseases such as hearing loss and tinnitus have become increasingly directed toward regenerative therapeutic approaches. This review discusses the currently most promising strategies for hair cell regeneration in the inner ear to treat hearing loss, including stem cell-based, gene transfer-based, and pharmacological interventions. Furthermore, previous milestones and ground-breaking work in this scientific field are identified...
January 2018: HNO
https://www.readbyqxmd.com/read/29284013/creating-a-stem-cell-niche-in-the-inner-ear-using-self-assembling-peptide-amphiphiles
#13
Akihiro J Matsuoka, Zafar A Sayed, Nicholas Stephanopoulos, Eric J Berns, Anil R Wadhwani, Zachery D Morrissey, Duncan M Chadly, Shun Kobayashi, Alexandra N Edelbrock, Tomoji Mashimo, Charles A Miller, Tammy L McGuire, Samuel I Stupp, John A Kessler
The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears...
2017: PloS One
https://www.readbyqxmd.com/read/29272992/from-otic-induction-to-hair-cell-production-pax2-egfp-cell-line-illuminates-key-stages-of-development-in-mouse-inner-ear-organoid-model
#14
Stacy A Schaefer, Atsuko Y Higashi, Benjamin Loomis, Thomas Schrepfer, Guoqiang Wan, Gabriel Corfas, Gregory R Dressler, Robert Keith Duncan
Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues resembling vestibular sensory epithelia-has sparked interest in applications such as regeneration, drug discovery, and disease modeling. In this study, we adapted this protocol for a novel mouse embryonic stem cell line with a fluorescent reporter for Pax2 expression...
February 15, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29236919/evidence-of-progenitor-cells-in-the-adult-human-cochlea-sphere-formation-and-identification-of-abcg2
#15
Milene Massucci-Bissoli, Karina Lezirovitz, Jeanne Oiticica, Ricardo Ferreira Bento
OBJECTIVES: The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2. METHODS: Cochleas removed from patients undergoing vestibular schwannoma resection (n=2) and from brain-dead organ donors (n=4) were dissociated for either flow cytometry analysis for the stem cell marker ABCG2 or a sphere formation assay that is widely used to test the sphere-forming capacity of cells from mouse inner ear tissue...
November 2017: Clinics
https://www.readbyqxmd.com/read/29214897/ss-31-peptide-enables-mitochondrial-targeting-drug-delivery-a-promising-therapeutic-alteration-to-prevent-hair-cell-damage-from-aminoglycosides
#16
Xiao Kuang, Shuang Zhou, Weiling Guo, Zhenjie Wang, Yanhui Sun, Hongzhuo Liu
Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#17
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
#18
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
#19
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
#20
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
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