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https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#1
REVIEW
Eduarda G Z Centeno, Helena Cimarosti, Angela Bithell
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results...
May 22, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783101/chondrogenic-differentiation-in-vitro-of-hipscs-activates-pathways-engaged-in-limb-development
#2
Ewelina Stelcer, Katarzyna Kulcenty, Marcin Rucinski, Karol Jopek, Magdalena Richter, Tomasz Trzeciak, Wiktoria Maria Suchorska
No abstract text is available yet for this article.
May 18, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29778976/developing-two-reference-control-samples-for-the-indian-population
#3
Shruti Iyer, Priyanka Bhatia, Mahendra Rao, Odity Mukherjee
Human induced Pluripotent Stem Cells (HiPSCs) have immense potential in research and therapeutics. Under the aegis of Department of Biotechnology funded national program entitled, "The Accelerator program for Discovery in Brain Disorders using Stem Cells (ADBS)" we have established a HiPSC biorepository (https://www.ncbs.res.in/adbs/bio-repository) with an objective to study severe mental illness. The repository comprises of HiPSC lines derived from healthy control donors and individuals with life time diagnosis of severe mental illness from dense families...
May 12, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29775723/a-scale-out-approach-towards-neural-induction-of-human-induced-pluripotent-stem-cells-for-neurodevelopmental-toxicity-studies
#4
Cláudia C Miranda, Tiago G Fernandes, Sandra N Pinto, Manuel Prieto, M Margarida Diogo, Joaquim M S Cabral
Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29770595/repair-potential-of-non-surgically-delivered-induced-pluripotent-stem-cell-derived-chondrocytes-in-a-rat-osteochondral-defect-model
#5
Yeri Alice Rim, Yoojun Nam, Narae Park, Jennifer Lee, Sung-Hwan Park, Ji Hyeon Ju
Human induced pluripotent stem cells (hiPSCs) are thought to be an alternative cell source for future regenerative medicine. hiPSCs may allow unlimited production of cell types that have low turnover rates and are difficult to obtain such as autologous chondrocytes. In this study, we generated hiPSC-derived chondrogenic pellets and chondrocytes were isolated. To confirm the curative effects, chondrogenic pellets and isolated chondrocytes were transplanted into rat joints with osteochondral defects. Isolated hiPSC-derived chondrocytes were delivered in the defect by a single intra-articular injection...
May 16, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29768213/mirnas-that-induce-human-cardiomyocyte-proliferation-converge-on-the-hippo-pathway
#6
Marta Diez-Cuñado, Ke Wei, Paul J Bushway, Mano R Maurya, Ranjan Perera, Shankar Subramaniam, Pilar Ruiz-Lozano, Mark Mercola
Understanding the mechanisms that control human cardiomyocyte proliferation might be applicable to regenerative medicine. We screened a whole genome collection of human miRNAs, identifying 96 to be capable of increasing proliferation (DNA synthesis and cytokinesis) of human iPSC-derived cardiomyocytes. Chemical screening and computational approaches indicated that most of these miRNAs (67) target different components of the Hippo pathway and that their activity depends on the nuclear translocation of the Hippo transcriptional effector YAP...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29763708/pcdh19-regulation-of-neural-progenitor-cell-differentiation-suggests-asynchrony-of-neurogenesis-as-a-mechanism-contributing-to-pcdh19-girls-clustering-epilepsy
#7
Claire C Homan, Stephen Pederson, Thu-Hien To, Chuan Tan, Sandra Piltz, Mark Corbett, Ernst Wolvetang, Paul Thomas, Lachlan A Jolly, Jozef Gecz
PCDH19-Girls Clustering Epilepsy (PCDH19-GCE) is a childhood epileptic encephalopathy characterised by a spectrum of neurodevelopmental problems. PCDH19-GCE is caused by heterozygous loss-of-function mutations in the X-chromosome gene, Protocadherin 19 (PCDH19) encoding a cell-cell adhesion molecule. Intriguingly, hemizygous males are generally unaffected. As PCDH19 is subjected to random X-inactivation, heterozygous females are comprised of a mosaic of cells expressing either the normal or mutant allele, which is thought to drive pathology...
May 12, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29761384/a-simple-multistep-protocol-for-differentiating-human-induced-pluripotent-stem-cells-into-functional-macrophages
#8
Chandrayana Mukherjee, Christine Hale, Subhankar Mukhopadhyay
Macrophages differentiated from human induced pluripotent stem cells (hiPSCs) provide an alternative new tool overcoming some of the limitations of existing models for human macrophages, such as human macrophage-like cell lines and primary monocyte-derived macrophages. A combination of different cytokines and growth factors can differentiate hiPSCs toward myeloid lineage. Here we describe a simple multistep protocol for differentiating hiPSCs into functional macrophages. This includes derivation of three germ-line containing embryoid bodies (EBs) from iPSCs, generation of myeloid precursors from EBs, and finally maturation of myeloid precursors into functional macrophages...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29760741/establishing-a-surgical-procedure-for-rhesus-epiretinal-scaffold-implantation-with-hipsc-derived-retinal-progenitors
#9
Ziming Luo, Kang Li, Kaijing Li, Bikun Xian, Ying Liu, Sijing Yang, Chaochao Xu, Zhigang Fan, Shoutao Lu, Haijun Zhang, Jian Ge
Background: To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. Methods: Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space ( n = 50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange ( n = 1), tamponade by hydrogel ( n = 1), and fixation by retinal tacks ( n = 4), were performed in rhesus monkeys...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29758302/plasminogen-binding-inhibitors-demonstrate-unwanted-activities-on-gaba-a-and-glycine-receptors-in-human-ipsc-derived-neurons
#10
Lisbeth Kristensson, Anders Lundin, David Gustafsson, Jan Fryklund, Tomas Fex, Delsing Louise, Erik Ryberg
Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABAA and glycine receptors...
May 11, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29754959/human-induced-pluripotent-stem-cell-derived-cardiac-cell-sheets-expressing-genetically-encoded-voltage-indicator-for-pharmacological-and-arrhythmia-studies
#11
Naim Shaheen, Assad Shiti, Irit Huber, Rami Shinnawi, Gil Arbel, Amira Gepstein, Noga Setter, Idit Goldfracht, Amit Gruber, Snizhanna V Chorna, Lior Gepstein
Fulfilling the potential of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes for studying conduction and arrhythmogenesis requires development of multicellular models and methods for long-term repeated tissue phenotyping. We generated confluent hiPSC-derived cardiac cell sheets (hiPSC-CCSs), expressing the genetically encoded voltage indicator ArcLight. ArcLight-based optical mapping allowed generation of activation and action-potential duration (APD) maps, which were validated by mapping the same hiPSC-CCSs with the voltage-sensitive dye, Di-4-ANBDQBS...
May 7, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29752948/functional-and-transcriptomic-insights-into-pathogenesis-of-r9c-phospholamban-mutation-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#12
Delaine K Ceholski, Irene C Turnbull, Chi-Wing Kong, Simon Koplev, Joshua Mayourian, Przemek A Gorski, Francesca Stillitano, Angelos A Skodras, Mathieu Nonnenmacher, Ninette Cohen, Johan L M Björkegren, Daniel R Stroik, Razvan L Cornea, David D Thomas, Ronald A Li, Kevin D Costa, Roger J Hajjar
Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted β-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to β-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes...
May 9, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29751846/generation-of-three-dimensional-human-neuronal-cultures-application-to-modeling-cns-viral-infections
#13
Leonardo D'Aiuto, Jennifer Naciri, Nicholas Radio, Sesha Tekur, Dennis Clayton, Gerard Apodaca, Roberto Di Maio, Yun Zhi, Peter Dimitrion, Paolo Piazza, Matthew Demers, Joel Wood, Charleen Chu, Jason Callio, Lora McClain, Robert Yolken, James McNulty, Paul Kinchington, David Bloom, Vishwajit Nimgaonkar
BACKGROUND: A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29751772/expression-profiling-of-cell-intrinsic-regulators-in-the-process-of-differentiation-of-human-ipscs-into-retinal-lineages
#14
Jen-Hua Chuang, Aliaksandr A Yarmishyn, De-Kuang Hwang, Chih-Chien Hsu, Mong-Lien Wang, Yi-Ping Yang, Ke-Hung Chien, Shih-Hwa Chiou, Chi-Hsien Peng, Shih-Jen Chen
BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages. METHODS: In this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29751108/basal-glucocorticoid-receptor-activation-induces-proliferation-and-inhibits-neuronal-differentiation-of-human-induced-pluripotent-stem-cell-derived-neuronal-precursor-cells
#15
Elina Nürnberg, Sandra Horschitz, Patrick Schloss, Andreas Meyer-Lindenberg
Glucocorticoids (GC) have first been shown to originate from the adrenal glands where synthesis and release is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it was shown that GC and other steroid hormones are also synthesized in the central nervous system, so-called neurosteroids. GC bind to specific GC receptors (GR) which function as ligand-activated transcription factors. GR are expressed in nearly all cell types in the brain, and therefore GC have a strong impact on neuronal development...
May 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29748973/afm-nano-mechanical-study-of-the-beating-profile-of-hipsc-derived-cardiomyocytes-beating-bodies-wt-and-dm1
#16
S Dinarelli, M Girasole, P Spitalieri, R V Talarico, M Murdocca, A Botta, G Novelli, R Mango, F Sangiuolo, G Longo
Myotonic Dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, characterized by a variety of multisystemic features and associated with cardiac anomalies. Among cardiac phenomena, conduction defects, ventricular arrhythmias, and dilated cardiomyopathy represent the main cause of sudden death in DM1 patients. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful in vitro model for molecular, biochemical, and physiological studies of disease in the target cells...
May 10, 2018: Journal of Molecular Recognition: JMR
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
#17
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/29734702/a-cardiac-cell-outgrowth-assay-for-evaluating-drug-compounds-using-a-cardiac-spheroid-on-a-chip-device
#18
Jonas Christoffersson, Florian Meier, Henning Kempf, Kristin Schwanke, Michelle Coffee, Mario Beilmann, Robert Zweigerdt, Carl-Fredrik Mandenius
Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device...
May 4, 2018: Bioengineering
https://www.readbyqxmd.com/read/29731429/electrophysiologic-characterization-of-calcium-handling-in-human-induced-pluripotent-stem-cell-derived-atrial-cardiomyocytes
#19
Mariana Argenziano, Erin Lambers, Liang Hong, Arvind Sridhar, Meihong Zhang, Brandon Chalazan, Ambili Menon, Eleonora Savio-Galimberti, Joseph C Wu, Jalees Rehman, Dawood Darbar
Human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (CMs) hold great promise for elucidating underlying cellular mechanisms that cause atrial fibrillation (AF). In order to use atrial-like hiPSC-CMs for arrhythmia modeling, it is essential to better understand the molecular and electrophysiological phenotype of these cells. We performed comprehensive molecular, transcriptomic, and electrophysiologic analyses of retinoic acid (RA)-guided hiPSC atrial-like CMs and demonstrate that RA results in differential expression of genes involved in calcium ion homeostasis that directly interact with an RA receptor, chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII)...
April 28, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29730419/crispr-cas9-gene-editing-of-ryr2-in-human-stem-cell-derived-cardiomyocytes-provides-a-novel-approach-in-investigating-dysfunctional-ca-2-signaling
#20
Hua Wei, Xiao-Hua Zhang, Cassandra Clift, Naohiro Yamaguchi, Martin Morad
Type-2 ryanodine receptors (RyR2s) play a pivotal role in cardiac excitation-contraction coupling by releasing Ca2+ from sarcoplasmic reticulum (SR) via a Ca2+ -induced Ca2+ release (CICR) mechanism. Two strategies have been used to study the structure-function characteristics of RyR2 and its disease associated mutations: (1) heterologous cell expression of the recombinant mutant RyR2s, and (2) knock-in mouse models harboring RyR2 point mutations. Here, we establish an alternative approach where Ca2+ signaling aberrancy caused by the RyR2 mutation is studied in human cardiomyocytes with robust CICR mechanism...
April 27, 2018: Cell Calcium
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