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https://www.readbyqxmd.com/read/28441409/a-hypomorphic-piga-gene-mutation-causes-severe-defects-in-neuron-development-and-susceptibility-to-complement-mediated-toxicity-in-a-human-ipsc-model
#1
Xuan Yuan, Zhe Li, Andrea C Baines, Eleni Gavriilaki, Zhaohui Ye, Zhexing Wen, Evan M Braunstein, Leslie G Biesecker, Linzhao Cheng, Xinzhong Dong, Robert A Brodsky
Mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis underlie a group of congenital syndromes characterized by severe neurodevelopmental defects. GPI anchored proteins have diverse roles in cell adhesion, signaling, metabolism and complement regulation. Over 30 enzymes are required for GPI anchor biosynthesis and PIGA is involved in the first step of this process. A hypomorphic mutation in the X-linked PIGA gene (c.1234C>T) causes multiple congenital anomalies hypotonia seizure syndrome 2 (MCAHS2), indicating that even partial reduction of GPI anchored proteins dramatically impairs central nervous system development, but the mechanism is unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28434976/compartmentalized-microfluidic-perfusion-system-to-culture-human-induced-pluripotent-stem-cell-aggregates
#2
Yuki Kondo, Koji Hattori, Shota Tashiro, Eri Nakatani, Ryosuke Yoshimitsu, Taku Satoh, Shinji Sugiura, Toshiyuki Kanamori, Kiyoshi Ohnuma
Microfluidic perfusion systems enable small-volume cell cultures under precisely controlled microenvironments, and are typically developed for cell-based high-throughput screening. However, most such systems are designed to manipulate dissociated single cells, not cell aggregates, and are thus unsuitable to induce differentiation in human induced pluripotent stem cells (hiPSCs), which is conventionally achieved by using cell aggregates to increase cell-cell interactions. We have now developed a compartmentalized microfluidic perfusion system with large flow channels to load, culture, and observe cell aggregates...
April 20, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28430892/anti-arrhythmic-potential-of-the-late-sodium-current-inhibitor-gs-458967-in-murine-scn5a-1798insd-and-human-scn5a-1795insd-ipsc-derived-cardiomyocytes
#3
Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A M Wilde, Connie R Bezzina, Marieke W Veldkamp, Carol Ann Remme
AIM: Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#4
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28418023/human-induced-pluripotent-stem-cells-for-modelling-neurodevelopmental-disorders
#5
REVIEW
Karthikeyan Ardhanareeswaran, Jessica Mariani, Gianfilippo Coppola, Alexej Abyzov, Flora M Vaccarino
We currently have a poor understanding of the pathogenesis of neurodevelopmental disorders, owing to the fact that postmortem and imaging studies can only measure the postnatal status quo and offer little insight into the processes that give rise to the observed outcomes. Human induced pluripotent stem cells (hiPSCs) should, in principle, prove powerful for elucidating the pathways that give rise to neurodevelopmental disorders. hiPSCs are embryonic-stem-cell-like cells that can be derived from somatic cells...
April 18, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28396709/human-ipsc-derived-myocardium-on-chip-with-capillary-like-flow-for-personalized-medicine
#6
Bradley W Ellis, Aylin Acun, U Isik Can, Pinar Zorlutuna
The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current in vitro models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells...
March 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28395738/a-feeder-and-xeno-free-human-induced-pluripotent-stem-cell-line-obtained-from-primary-human-dermal-fibroblasts-with-epigenetic-repression-of-reprogramming-factors-expression-gpcci001-a
#7
Michał Stefan Lach, Joanna P Wroblewska, Ewelina Augustyniak, Katarzyna Kulcenty, Wiktoria Maria Suchorska
The primary human dermal fibroblasts (PHDFs) from breast cancer patient were obtained to generate the human induced pluripotent stem cell line GPCCi001-A via lentiviral transfection. Thus, a modified EF1a-hSTEMCCA-loxP with tetO operator which regulates transgene expression was used. This method takes advantage of epigenetic regulation of transcription and allows for stable silencing of the reprogramming factors in obtained hiPS cells. To increase the potential utility of hiPSCs for clinical applications, they were adapted to feeder- and xeno-free conditions...
April 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395736/generation-of-an-induced-pluripotent-stem-cell-line-from-a-loeys-dietz-syndrome-patient-with-transforming-growth-factor-beta-receptor-2-gene-mutation
#8
Kui Hu, Jun Li, Kai Zhu, Jinmiao Chen, Dingqian Liu, Yulin Wang, Yongxin Sun, Hao Lai, Chunsheng Wang
Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective tissue disorder, commonly caused by genetic mutation of transforming growth factor-beta receptor (TGFBR)-1 or TGFBR2. This study describes the generation of human induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells obtained from an LDS patient with TGFBR2 mutation (R193W). Analysis confirmed the cells had a normal karyotype, expressed typical pluripotency markers, had the ability to differentiate into all three germ layers in vivo, and retained the TGFBR2 mutation from the derived hiPSCs...
April 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28388432/large-diverse-population-cohorts-of-hipscs-and-derived-hepatocyte-like-cells-reveal-functional-genetic-variation-at-blood-lipid-associated-loci
#9
Evanthia E Pashos, YoSon Park, Xiao Wang, Avanthi Raghavan, Wenli Yang, Deepti Abbey, Derek T Peters, Juan Arbelaez, Mayda Hernandez, Nicolas Kuperwasser, Wenjun Li, Zhaorui Lian, Ying Liu, Wenjian Lv, Stacey L Lytle-Gabbin, Dawn H Marchadier, Peter Rogov, Jianting Shi, Katherine J Slovik, Ioannis M Stylianou, Li Wang, Ruilan Yan, Xiaolan Zhang, Sekar Kathiresan, Stephen A Duncan, Tarjei S Mikkelsen, Edward E Morrisey, Daniel J Rader, Christopher D Brown, Kiran Musunuru
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96)...
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28388226/a-review-of-research-grade-human-induced-pluripotent-stem-cells-qualification-and-biobanking-processes
#10
Aikaterini Ntai, Simona Baronchelli, Alberto La Spada, Anna Moles, Alessandro Guffanti, Pasquale De Blasio, Ida Biunno
Human induced pluripotent stem cell (hiPSC) biobanks are invaluable resources for basic and clinical research, since they provide a sustainable supply of accessible cell lines that meet high quality and safety standards. hiPSCs are particularly useful for understanding disease mechanisms, creating cell models for drug development, and generating novel clinical therapies. For clinical applications and drug discovery, it is fundamental that the acquired pluripotent cell lines never touch animal-derived products nor xenogeneic reagents (Good Manufacturing Practice-grade); whereas for research grade, it is sufficient to operate under Good Laboratory Practice conditions...
April 7, 2017: Biopreservation and Biobanking
https://www.readbyqxmd.com/read/28387893/regenerative-medicine-in-cardiovascular-diseases-an-update
#11
Y Cao, P-Y Zhang
The unique ability of regenerative medicine to differentiate into any cell of the three germ layers (endoderm, ectoderm, and mesoderm) is of immense clinical importance. They have an unique capacity for unlimited self-renewal. Furthermore, pluripotent stem cells (PSC), including human embryonic (hESC) and induced pluripotent stem cells (hiPSCs), hold great potential as an unlimited source of functional as well as transplantable cells applications. Specifically, in the context of cardiovascular and ischemic diseases, it is believed that hESC-derived endothelial cells (hESC- ECs) could be used to stimulate angiogenesis or vasculogenesis in ischemic tissues, thereby restoring blood supply to the affected area...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28384492/contractile-force-generation-by-3d-hipsc-derived-cardiac-tissues-is-enhanced-by-rapid-establishment-of-cellular-interconnection-in-matrix-with-muscle-mimicking-stiffness
#12
Soah Lee, Vahid Serpooshan, Xinming Tong, Sneha Venkatraman, Meelim Lee, Jaecheol Lee, Orlando Chirikian, Joseph C Wu, Sean M Wu, Fan Yang
Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28384403/high-density-individually-addressable-nanowire-arrays-record-intracellular-activity-from-primary-rodent-and-human-stem-cell-derived-neurons
#13
Ren Liu, Renjie Chen, Ahmed T E Youssef, Sang Heon Lee, Sandy Hinckley, Massoud L Khraiche, John Scott, Deborah Pre, Yoontae Hwang, Atsunori Tanaka, Yun Goo Ro, Albert Keisuke Matsushita, Xing Dai, Cesare Soci, Steven Biesmans, Anthony R James, John Nogan, Katherine L Jungjohann, Douglas V Pete, Denise B Webb, Yimin Zou, Anne G Bang, Shadi A Dayeh
We report a new hybrid integration scheme that offers for the first time a nanowire-on-lead approach which enables independent electrical addressability, is scalable, and has superior spatial resolution in vertical nanowire arrays. The fabrication of these nanowire arrays is demonstrated to be scalable down to submicrometer site-to-site spacing, and can be combined with standard integrated circuit fabrication technologies. We utilize these arrays to perform electrophysiological recordings from mouse and rat primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons which revealed high signal to noise ratios and sensitivity to subthreshold postsynaptic potentials (PSPs)...
April 6, 2017: Nano Letters
https://www.readbyqxmd.com/read/28382727/scalable-stirred-suspension-culture-for-the-generation-of-billions-of-human-induced-pluripotent-stem-cells-using-single-use-bioreactors
#14
Chee Keong Kwok, Yuichiro Ueda, Asifiqbal Kadari, Katharina Günther, Antoine Heron, Aletta C Schnitzler, Martha Rook, Frank Edenhofer
The production of human induced pluripotent stem cells (hiPSCs) in quantities that are relevant for cell-based therapies and cell-loaded implants through standard adherent culture is hardly achievable and lacks process scalability. A promising approach to overcoming these hurdles is the culture of hiPSCs in suspension. In this study, stirred suspension culture vessels were investigated for their suitability in the expansion of two hiPSC lines inoculated as a single cell suspension, with a free scalability between volumes of 50 and 2 400 mL...
April 6, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28377112/the-assessment-of-electrophysiological-activity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-exposed-to-dimethyl-sulfoxide-and-ethanol-by-manual-patch-clamp-and-multi-electrode-array-system
#15
Soo-Wang Hyun, Bo-Ram Kim, Sung-Ae Hyun, Joung-Wook Seo
INTRODUCTION: Recently, electrophysiological activity has been effectively measured in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to predict drug-induced arrhythmia. Dimethyl sulfoxide (DMSO) and ethanol have been used as diluting agents in many experiments. However, the maximum DMSO and ethanol concentrations that can be effectively used in the measurement of electrophysiological parameters in hiPSC-CMs-based patch clamp and multi-electrode array (MEA) have not been fully elucidated...
April 1, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28376365/bioacoustic-enabled-patterning-of-human-ipsc-derived-cardiomyocytes-into-3d-cardiac-tissue
#16
Vahid Serpooshan, Pu Chen, Haodi Wu, Soah Lee, Arun Sharma, Daniel A Hu, Sneha Venkatraman, Adarsh Venkataraman Ganesan, Osman Berk Usta, Martin Yarmush, Fan Yang, Joseph C Wu, Utkan Demirci, Sean M Wu
The creation of physiologically-relevant human cardiac tissue with defined cell structure and function is essential for a wide variety of therapeutic, diagnostic, and drug screening applications. Here we report a new scalable method using Faraday waves to enable rapid aggregation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into predefined 3D constructs. At packing densities that approximate native myocardium (10(8)-10(9) cells/ml), these hiPSC-CM-derived 3D tissues demonstrate significantly improved cell viability, metabolic activity, and intercellular connection when compared to constructs with random cell distribution...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28368043/impact-of-cell-composition-and-geometry-on-human-induced-pluripotent-stem-cells-derived-engineered-cardiac-tissue
#17
Takeichiro Nakane, Hidetoshi Masumoto, Joseph P Tinney, Fangping Yuan, William J Kowalski, Fei Ye, Amanda J LeBlanc, Ryuzo Sakata, Jun K Yamashita, Bradley B Keller
The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28366443/modeling-the-mutational-and-phenotypic-landscapes-of-pelizaeus-merzbacher-disease-with-human-ipsc-derived-oligodendrocytes
#18
Zachary S Nevin, Daniel C Factor, Robert T Karl, Panagiotis Douvaras, Jeremy Laukka, Martha S Windrem, Steven A Goldman, Valentina Fossati, Grace M Hobson, Paul J Tesar
Pelizaeus-Merzbacher disease (PMD) is a pediatric disease of myelin in the central nervous system and manifests with a wide spectrum of clinical severities. Although PMD is a rare monogenic disease, hundreds of mutations in the X-linked myelin gene proteolipid protein 1 (PLP1) have been identified in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes. To address this, we generated panels of human induced pluripotent stem cells (hiPSCs) and hiPSC-derived oligodendrocytes from 12 individuals with mutations spanning the genetic and clinical diversity of PMD-including point mutations and duplication, triplication, and deletion of PLP1-and developed an in vitro platform for molecular and cellular characterization of all 12 mutations simultaneously...
April 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28361319/making-a-kidney-organoid-using-the-directed-differentiation-of-human-pluripotent-stem-cells
#19
Minoru Takasato, Melissa H Little
An organoid can be defined as a three-dimensional organ-like structure formed from organ-specific progenitor cells. Organ progenitor cells were empirically found to self-organize three-dimensional tissues when they were aggregated and cultivated in vitro. While this nature power of progenitor cells has an amazing potential to recreate artificial organs in vitro, there had been difficulty to apply this technology to human organs due to the inaccessibility to human progenitor cells until human-induced pluripotent stem cell (hiPSC) was invented by Takahashi and Yamanaka in 2007...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28353258/stem-cell-banking-a-global-view
#20
Glyn Stacey
Stem cell banking has been a topic of discussion and debate for more than a decade since the first public services to supply human embryonic stem cells (hESCs) were established in the USA and the UK. This topic has received a recent revival with numerous ambitious programmes announced to deliver large collections of human induced pluripotency cell (hiPSC) lines. This chapter will provide a brief overview charting the development of stem cell banks, their value, and their likely role in the future.
2017: Methods in Molecular Biology
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