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https://www.readbyqxmd.com/read/28746822/astrocyte-enriched-feeder-layers-from-cryopreserved-cells-support-differentiation-of-spontaneously-active-networks-of-human-ipsc-derived-neurons
#1
Ryan J Schutte, Yunyao Xie, Nathan N Ng, Priscilla Figueroa, An T Pham, Diane K O'Dowd
BACKGROUND: Human induced pluripotent stem cell (hiPSC)-derived neuronal cultures are a useful tool for studying the mechanisms of neurological disorders and developing novel therapeutics. While plating hiPSC-derived neuronal progenitors onto glial feeder layers prepared from rodent cortex has been reported to promote functional differentiation of neuronal networks, this has not been examined in detail. NEW METHOD: Here we describe a method of using cryopreserved cells from primary cultures for generation of mouse astrocyte-enriched, neuron-free feeder layers that grow from 10% to 100% confluence in 1 week...
July 23, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28746394/effects-of-oxidative-and-thermal-stresses-on-stress-granule-formation-in-human-induced-pluripotent-stem-cells
#2
Freshteh Palangi, Samson M Samuel, I Richard Thompson, Chris R Triggle, Mohamed M Emara
Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated. Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H2O2), induce SG formation in human induced (hi) PSCs. Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress...
2017: PloS One
https://www.readbyqxmd.com/read/28745632/differentiating-chondrocytes-from-peripheral-blood-derived-human-induced-pluripotent-stem-cells
#3
Yueying Li, Yong Hai, Jiayu Chen, Tie Liu
In this study, we used peripheral blood cells (PBCs) as seed cells to produce chondrocytes via induced pluripotent stem cells (iPSCs) in an integration-free method. Following embryoid body (EB) formation and fibroblastic cell expansion, the iPSCs are induced for chondrogenic differentiation for 21 days under serum-free and xeno-free conditions. After chondrocyte induction, the phenotypes of the cells are evaluated by morphological, immunohistochemical, and biochemical analyses, as well as by the quantitative real-time PCR examination of chondrogenic differentiation markers...
July 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28742076/altered-neurite-morphology-and-cholinergic-function-of-induced-pluripotent-stem-cell-derived-neurons-from-a-patient-with-kleefstra-syndrome-and-autism
#4
J Nagy, J Kobolák, S Berzsenyi, Z Ábrahám, H X Avci, I Bock, Z Bekes, B Hodoscsek, A Chandrasekaran, A Téglási, P Dezső, B Koványi, E T Vörös, L Fodor, T Szél, K Németh, A Balázs, A Dinnyés, B Lendvai, G Lévay, V Román
The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells...
July 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28740258/mechanically-stable-fibrin-scaffolds-promote-viability-and-induce-neurite-outgrowth-in-neural-aggregates-derived-from-human-induced-pluripotent-stem-cells
#5
Meghan Robinson, Sarah Douglas, Stephanie Michelle Willerth
Recent work demonstrated that 3D fibrin scaffolds function as an effective substrate for engineering tissues from pluripotent stem cells. However, the rapid degradation rate of fibrin remains a major limitation when differentiating human pluripotent stem cells for tissue engineering applications. The addition of crosslinking agents, such as genipin, during the polymerization process increases scaffold stability while decreasing the degradation rate of fibrin. Genipin crosslinking alters the physical characteristics of the fibrin scaffolds, which influences the behaviour of the differentiating cells seeded inside...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28735524/characterization-of-cytoskeleton-features-and-maturation-status-of-cultured-human-ipsc-derived-cardiomyocytes
#6
Christian Zuppinger, George Gibbons, Priyanka Dutta-Passecker, Adrian Segiser, Henriette Most, Thomas M Suter
Recent innovations in stem cell technologies and the availability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have opened new possibilities for studies and drug testing on human cardiomyocytes in vitro. Still, there are concerns about the precise nature of such 'reprogrammed' cells. We have performed an investigation using immunocytochemistry and confocal microscopy on several cellular features using commercially available hiPSC-CMs. For some selected developmentally regulated or cardiac chamber-specific proteins, we have compared the results from hiPSC-derived cardiomyocytes with freshly isolated, ventricular cardiomyocytes from adult rats...
June 21, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28732597/pattern-of-gene-expression-in-different-stages-of-schizophrenia-down-regulation-of-nptx2-gene-revealed-by-a-meta-analysis-of-microarray-datasets
#7
Mirko Manchia, Ignazio S Piras, Matthew J Huentelman, Federica Pinna, Clement C Zai, James L Kennedy, Bernardo Carpiniello
Schizophrenia (SCZ) is a severe psychiatric disorder with a genetic susceptibility. Alterations in neurochemical signaling, as well as changes in brain structure and function, manifest during the course of SCZ and are likely causative of the symptoms shown by affected individuals. However, little is known about the timing of these changes, particularly in the pre-morbid and prodromal phases of SCZ. Here, we performed a gene-based and pathway-based meta-analysis of 5 microarray datasets from human induced pluripotent stem cells (hiPSCs)-derived neurons and post-mortem brain tissue from SCZ and healthy controls (HC), with the underlying assumption they might represent the neurobiological make-up of SCZ in the pre-morbid and chronic stages of illness, respectively...
July 18, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28732246/inspiration-from-heart-development-biomimetic-development-of-functional-human-cardiac-organoids
#8
Dylan J Richards, Robert C Coyle, Yu Tan, Jia Jia, Kerri Wong, Katelynn Toomer, Donald R Menick, Ying Mei
Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28729840/cardiac-subtype-specific-modeling-of-kv1-5-ion-channel-deficiency-using-human-pluripotent-stem-cells
#9
Maike Marczenke, Ilaria Piccini, Isabella Mengarelli, Jakob Fell, Albrecht Röpke, Guiscard Seebohm, Arie O Verkerk, Boris Greber
The ultrarapid delayed rectifier K(+) current (IKur), mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729666/expansion-of-human-midbrain-floor-plate-progenitors-from-induced-pluripotent-stem-cells-increases-dopaminergic-neuron-differentiation-potential
#10
Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726548/wnt-yap-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#11
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28725655/cell-replacement-therapy-is-the-remedial-solution-for-treating-parkinson-s-disease
#12
REVIEW
Venkatesan Dhivya, Vellingiri Balachandar
The selective degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) has made an idol target for cell replacement therapies and other emerging surgical treatments. Certainly, by transplantation method, the therapeutic regimens such as human fetal ventral midbrain (hfVM) cells, human embryonic stem cells (hESCs), human neural stem/precursor/ progenitor cells (hNSCs/hNPCs), human mesenchymal stem cells (hMSCs), human induced neural stem cells (hiNSCs), and human induced pluripotent stem cells (hiPSCs) have been used into DA deficient striatum...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28721524/human-ipsc-derived-cardiomyocytes-for-investigation-of-disease-mechanisms-and-therapeutic-strategies-in-inherited-arrhythmia-syndromes-strengths-and-limitations
#13
Simona Casini, Arie O Verkerk, Carol Ann Remme
During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies...
July 18, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28718622/graphene-sheet-induced-global-maturation-of-cardiomyocytes-derived-from-human-induced-pluripotent-stem-cells
#14
Jiaxian Wang, Chang Cui, Haiyan Nan, Yuanfang Yu, Yini Xiao, Ellen Poon, Gang Yang, Xijie Wang, Chenchen Wang, Lingsong Li, Kenneth Richard Boheler, Xu Ma, Xin Cheng, Zhenhua Ni, Minglong Chen
Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, or physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate, which is a biocompatible and superconductive material...
July 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28717982/characterization-of-zinc-amino-acid-complexes-for-zinc-delivery-in-vitro-using-caco-2-cells-and-enterocytes-from-hipsc
#15
Ann Katrin Sauer, Stefanie Pfaender, Simone Hagmeyer, Laura Tarana, Ann-Kathrin Mattes, Franziska Briel, Sébastien Küry, Tobias M Boeckers, Andreas M Grabrucker
Zn is essential for growth and development. The bioavailability of Zn is affected by several factors such as other food components. It is therefore of interest, to understand uptake mechanisms of Zn delivering compounds to identify ways to bypass the inhibitory effects of these factors. Here, we studied the effect of Zn amino acid conjugates (ZnAAs) on the bioavailabilty of Zn. We used Caco-2 cells and enterocytes differentiated from human induced pluripotent stem cells from a control and Acrodermatitis enteropathica (AE) patient, and performed fluorescence based assays, protein biochemistry and atomic absorption spectrometry to characterize cellular uptake and absorption of ZnAAs...
July 17, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28717970/prostaglandin-ep2-receptors-mediate-mesenchymal-stromal-cell-neuroprotective-effects-on-dopaminergic-neurons
#16
Juan Andrés Parga, María García-Garrote, Salvador Martínez, Ángel Raya, José Luis Labandeira-García, Jannette Rodríguez-Pallares
Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson's disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM)...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28717411/skeletal-muscle-generated-from-induced-pluripotent-stem-cells-induction-and-application
#17
REVIEW
Yuko Miyagoe-Suzuki, Shin'ichi Takeda
Human induced pluripotent stem cells (hiPS cells or hiPSCs) can be derived from cells of patients with severe muscle disease. If skeletal muscle induced from patient-iPSCs shows disease-specific phenotypes, it can be useful for studying the disease pathogenesis and for drug development. On the other hand, human iPSCs from healthy donors or hereditary muscle disease-iPSCs whose genomes are edited to express normal protein are expected to be a cell source for cell therapy. Several protocols for the derivation of skeletal muscle from human iPSCs have been reported to allow the development of efficient treatments for devastating muscle diseases...
June 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28717111/usefulness-of-cardiotoxicity-assessment-using-calcium-transient-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
Hitoshi Watanabe, Yayoi Honda, Jiro Deguchi, Toru Yamada, Kiyoko Bando
Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716551/application-of-human-induced-pluripotent-stem-cells-to-model-fibrodysplasia-ossificans-progressiva
#19
Emilie Barruet, Edward C Hsiao
Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients with mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28711757/cxcr4-and-cxcr7-play-distinct-roles-in-cardiac-lineage-specification-and-pharmacologic-%C3%AE-adrenergic-response
#20
Delaine K Ceholski, Irene C Turnbull, Venu Pothula, Laura Lecce, Andrew A Jarrah, Changwon Kho, Ahyoung Lee, Lahouaria Hadri, Kevin D Costa, Roger J Hajjar, Sima T Tarzami
CXCR4 and CXCR7 are prominent G protein-coupled receptors (GPCRs) for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). This study demonstrates that CXCR4 and CXCR7 induce differential effects during cardiac lineage differentiation and β-adrenergic response in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-CMs were tested for phenotypic and functional properties due to gene knockdown. Gene expression and flow cytometry confirmed the pluripotent and cardiomyocyte phenotype of undifferentiated and differentiated hiPSCs, respectively...
July 8, 2017: Stem Cell Research
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