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Induced pluripotent

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https://www.readbyqxmd.com/read/29791859/combining-ngn2-programming-with-developmental-patterning-generates-human-excitatory-neurons-with-nmdar-mediated-synaptic-transmission
#1
Ralda Nehme, Emanuela Zuccaro, Sulagna Dia Ghosh, Chenchen Li, John L Sherwood, Olli Pietilainen, Lindy E Barrett, Francesco Limone, Kathleen A Worringer, Sravya Kommineni, Ying Zang, Davide Cacchiarelli, Alex Meissner, Rolf Adolfsson, Stephen Haggarty, Jon Madison, Matthias Muller, Paola Arlotta, Zhanyan Fu, Guoping Feng, Kevin Eggan
Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report that combining NGN2 programming with SMAD and WNT inhibition generates human patterned induced neurons (hpiNs). Single-cell analyses showed that hpiN cultures contained cells along a developmental continuum, ranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791489/contractile-force-measurement-of-human-induced-pluripotent-stem-cell-derived-cardiac-cell-sheet-tissue
#2
Daisuke Sasaki, Katsuhisa Matsuura, Hiroyoshi Seta, Yuji Haraguchi, Teruo Okano, Tatsuya Shimizu
We have developed our original tissue engineering technology "cell sheet engineering" utilizing temperature-responsive culture dishes. The cells are confluently grown on a temperature-responsive culture dish and can be harvested as a cell sheet by lowering temperature without enzymatic digestion. Cell sheets are high-cell-density tissues similar to actual living tissues, maintaining their structure and function. Based on this "cell sheet engineering", we are trying to create functional cardiac tissues from human induced pluripotent stem cells, for regenerative therapy and in vitro drug testing...
2018: PloS One
https://www.readbyqxmd.com/read/29790422/autologous-induced-pluripotent-stem-cell-derived-neurons-to-treat-parkinson-s-disease
#3
Jeanne F Loring
In 2012, we planned a program to develop a neuron replacement therapy for Parkinson's disease (PD) that would have the greatest promise to help the patients. PD is a movement disorder caused by the progressive, inevitable loss of a specific type of dopamine neuron in the brain. The only viable treatment to reverse the progress of the disease is to replace those neurons; we decided to make dopamine neurons that matched the patients, by differentiating induced pluripotent stem cells (iPSCs) that we generated from individuals with PD...
May 23, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29789581/intron-retention-and-nuclear-loss-of-sfpq-are-molecular-hallmarks-of-als
#4
Raphaelle Luisier, Giulia E Tyzack, Claire E Hall, Jamie S Mitchell, Helen Devine, Doaa M Taha, Bilal Malik, Ione Meyer, Linda Greensmith, Jia Newcombe, Jernej Ule, Nicholas M Luscombe, Rickie Patani
Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate ubiquitously expressed regulators of RNA processing. To understand the molecular impact of ALS-causing mutations on neuronal development and disease, we analysed transcriptomes during in vitro differentiation of motor neurons (MNs) from human control and patient-specific VCP mutant induced-pluripotent stem cells (iPSCs). We identify increased intron retention (IR) as a dominant feature of the splicing programme during early neural differentiation...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#5
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/29787427/impact-of-ionizing-radiation-on-electrophysiological-behavior-of-human-induced-ipsc-derived-cardiomyocytes-on-multielectrode-arrays
#6
Benjamin V Becker, Thomas Seeger, Thomas Beiert, Markus Antwerpen, Andreas Palnek, Matthias Port, Reinhard Ullmann
Cardiac arrhythmia presumably induced through cardiac fibrosis is a recurrent long-term consequence of exposure to ionizing radiation. However, there is also evidence that cardiac arrhythmia can occur in patients shortly after irradiation. In this study, the authors employed multielectrode arrays to investigate the short-term effects of x-ray radiation on the electrophysiological behavior of cardiomyocytes derived from human-induced pluripotent stem cells. These cardiomyocytes with spontaneous pacemaker activity were cultured on single-well multielectrode arrays...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#7
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786556/assessment-of-stem-cell-differentiation-based-on-genome-wide-expression-profiles
#8
REVIEW
Patricio Godoy, Wolfgang Schmidt-Heck, Birte Hellwig, Patrick Nell, David Feuerborn, Jörg Rahnenführer, Kathrin Kattler, Jörn Walter, Nils Blüthgen, Jan G Hengstler
In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786554/a-human-ipsc-line-capable-of-differentiating-into-functional-macrophages-expressing-zsgreen-a-tool-for-the-study-and-in-vivo-tracking-of-therapeutic-cells
#9
Martha Lopez-Yrigoyen, Antonella Fidanza, Luca Cassetta, Richard A Axton, A Helen Taylor, Jose Meseguer-Ripolles, Anestis Tsakiridis, Valerie Wilson, David C Hay, Jeffrey W Pollard, Lesley M Forrester
We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786550/generation-of-defined-neural-populations-from-pluripotent-stem-cells
#10
REVIEW
Sarah F McComish, Maeve A Caldwell
Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS)...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#11
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786548/designer-human-tissue-coming-to-a-lab-near-you
#12
David C Hay, Cliona O'Farrelly
Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784997/mechanics-guided-embryonic-patterning-of-neuroectoderm-tissue-from-human-pluripotent-stem-cells
#13
Xufeng Xue, Yubing Sun, Agnes M Resto-Irizarry, Ye Yuan, Koh Meng Aw Yong, Yi Zheng, Shinuo Weng, Yue Shao, Yimin Chai, Lorenz Studer, Jianping Fu
Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo...
May 21, 2018: Nature Materials
https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#14
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29781367/human-stem-cell-derived-models-lessons-for-autoimmune-diseases-of-the-nervous-system
#15
Oliver Harschnitz
Autoimmunity of the peripheral and central nervous system is an important cause of disease and long-term neurological disability. Autoantibodies can target both intracellular and extracellular neuronal epitopes. Autoantibodies that target cell-surface epitopes infer pathogenicity through several distinct mechanisms, while patients often respond to immunotherapy. However, the underlying pathogenesis of these autoantibodies is yet to be fully understood. Human stem cell-based disease modeling, and the rise of induced pluripotent stem cell technology in particular, has revolutionized the fields of disease modeling and therapeutic screening for neurological disorders...
May 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/29781336/advances-in-the-treatment-of-severe-alcoholic-hepatitis
#16
Wenjun Wang, Ying Xu, Chang Jiang, Yanhang Gao
Severe alcoholic hepatitis (SAH) is a costly and worldwide public health issue with high morbidity and mortality. Specific effective treatments for SAH have yet to be established. The aim of the present article is to review the current knowledge of the pathogenesis, assessment, and treatment options in patients with SAH. To date, alcohol abstinence and enteral nutrition are the recommended first-line treatments. Although corticosteroids remain the preferred therapy for certain patients with a modified Maddrey discriminant function level greater than 54, they only improve short-term survival rates...
May 21, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29781215/strap-deficiency-impairs-mouse-embryonic-stem-cells-lineage-commitment-through-cyp26a1-mediated-retinoic-acid-homeostasis
#17
Lin Jin, Chenbei Chang, Kevin M Pawlik, Arunima Datta, Larry M Johnson, Trung Vu, Joseph L Napoli, Pran K Datta
Retinoic acid (RA) signaling is essential for the differentiation of embryonic stem cells (ESCs) and vertebrate development. RA biosynthesis and metabolism are controlled by a series of enzymes, but the molecular regulators of these enzymes remain largely obscure. In this study, we investigated the functional role of the WD-domain protein STRAP (serine threonine kinase receptor-associated protein) in the pluripotency and lineage commitment of murine ESCs. We generated Strap knockout (KO) mouse ESCs and subjected them to spontaneous differentiation...
May 21, 2018: Stem Cells
https://www.readbyqxmd.com/read/29780049/-6-application-of-mri-technology-to-the-regenerative-medicine-in-heart-disease-using-induced-pluripotent-stem-cells
#18
Atsushi Tachibana
No abstract text is available yet for this article.
2018: Nihon Hoshasen Gijutsu Gakkai Zasshi
https://www.readbyqxmd.com/read/29780042/long-term-culture-of-human-ips-cell-derived-telencephalic-neuron-aggregates-on-collagen-gel
#19
Hiroshi Oyama, Koji Takahashi, Yoshikazu Tanaka, Hiroshi Takemoto, Hisashi Haga
It takes several months to form the 3-dimensional morphology of the human embryonic brain. Therefore, establishing a long-term culture method for neuronal tissues derived from human induced pluripotent stem (iPS) cells is very important for studying human brain development. However, it is difficult to keep primary neurons alive for more than 3 weeks in culture. Moreover, long-term adherent culture to maintain the morphology of telencephalic neuron aggregates induced from human iPS cells is also difficult. Although collagen gel has been widely used to support long-term culture of cells, it is not clear whether human iPS cell-derived neuron aggregates can be cultured for long periods on this substrate...
2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29779897/inductive-and-selective-effects-of-gsk3-and-mek-inhibition-on-nanog-heterogeneity-in-embryonic-stem-cells
#20
Simon Hastreiter, Stavroula Skylaki, Dirk Loeffler, Andreas Reimann, Oliver Hilsenbeck, Philipp S Hoppe, Daniel L Coutu, Konstantinos D Kokkaliaris, Michael Schwarzfischer, Konstantinos Anastassiadis, Fabian J Theis, Timm Schroeder
Embryonic stem cells (ESCs) display heterogeneous expression of pluripotency factors such as Nanog when cultured with serum and leukemia inhibitory factor (LIF). In contrast, dual inhibition of the signaling kinases GSK3 and MEK (2i) converts ESC cultures into a state with more uniform and high Nanog expression. However, it is so far unclear whether 2i acts through an inductive or selective mechanism. Here, we use continuous time-lapse imaging to quantify the dynamics of death, proliferation, and Nanog expression in mouse ESCs after 2i addition...
May 10, 2018: Stem Cell Reports
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