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stem cell disease modelling

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https://www.readbyqxmd.com/read/29923090/evaluation-of-disease-lesions-in-the-developing-canine-mps-iiia-brain
#1
Leanne K Winner, Neil R Marshall, Robert D Jolly, Paul J Trim, Stephen K Duplock, Marten F Snel, Kim M Hemsley
Mucopolysaccharidosis IIIA (MPS IIIA) is an inherited neurodegenerative disease of childhood that results in early death. Post-mortem studies have been carried out on human MPS IIIA brain, but little is known about early disease development. Here, we utilised the Huntaway dog model of MPS IIIA to evaluate disease lesion development from 2 to 24 weeks of age. A significant elevation in primarily stored heparan sulphate was observed in all brain regions assessed in MPS IIIA pups ≤9.5 weeks of age. There was a significant elevation in secondarily stored ganglioside (GM3 36:1) in ≤9...
June 20, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29922594/cancer-stem-cell-metabolism-and-potential-therapeutic-targets
#2
REVIEW
Vusala Snyder, Tamika C Reed-Newman, Levi Arnold, Sufi Mary Thomas, Shrikant Anant
Malignant tumors contain heterogeneous populations of cells in various states of proliferation and differentiation. The presence of cancer stem or initiating cells is a well-established concept wherein quiescent and poorly differentiated cells within a tumor mass contribute to drug resistance, and under permissive conditions, are responsible for tumor recurrence and metastasis. A number of studies have identified molecular markers that are characteristic of tissue-specific cancer stem cells (CSCs). Isolation of CSCs has enabled studies on the metabolic status of CSCs...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29921843/detection-of-genetic-cardiac-diseases-by-ca-2-transient-profiles-using-machine-learning-methods
#3
Martti Juhola, Henry Joutsijoki, Kirsi Penttinen, Katriina Aalto-Setälä
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have revolutionized cardiovascular research. Abnormalities in Ca2+ transients have been evident in many cardiac disease models. We have shown earlier that, by exploiting computational machine learning methods, normal Ca2+ transients corresponding to healthy CMs can be distinguished from diseased CMs with abnormal transients. Here our aim was to study whether it is possible to separate different genetic cardiac diseases (CPVT, LQT, HCM) on the basis of Ca2+ transients using machine learning methods...
June 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29921651/safety-and-efficacy-of-intracoronary-infusion-of-allogeneic-human-cardiac-stem-cells-in-patients-with-st-segment-elevation-myocardial-infarction-and-left-ventricular-dysfunction-a-multicenter-randomized-double-blind-and-placebo-controlled-clinical-trial
#4
Francisco Fernández-Avilés, Ricardo Sanz-Ruiz, Jan Bogaert, Ana Casado Plasencia, Inmaculada Gilaberte, Ann Belmans, María Eugenia Fernández-Santos, Dominique Charron, Miguel Mulet, Raquel Yotti, Itziar Palacios, Manuel Luque, Rafael Sádaba, J A San Roman, Mariano Larman, Pedro L Sánchez, Juan Sanchis, Manuel F Jimenez-Navarro, Piet Claus, Reem Al-Daccak, Eleuterio Lombardo, José Luis Abad, Olga Delarosa, Lucia Corcostegui, Javier Bermejo, Stefan Janssens
<u>Rationale:</u> Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory and regenerative properties with a robust safety profile in large animal models of heart disease. <u>Objective:</u> To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment elevation myocardial infarction (STEMI). <u>Methods and Results:</u> CAREMI was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with STEMI, LVEF ≤ 45% and infarct size ≥ 25% of left ventricular (LV) mass by cardiac magnetic resonance (MR), who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at day 5-7...
June 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29917042/generation-and-primary-characterization-of-iam-1-a-versatile-new-line-of-conditionally-immortalized-atrial-myocytes-with-preserved-cardiomyogenic-differentiation-capacity
#5
Jia Liu, Linda Volkers, Wanchana Jangsangthong, Cindy I Bart, Marc C Engels, Guangqian Zhou, Martin J Schalij, Dirk L Ypey, Daniël A Pijnappels, Antoine A F de Vries
Aims: The generation of homogeneous cardiomyocyte populations from fresh tissue or stem cells is laborious and costly. A potential solution to this problem would be to establish lines of immortalized cardiomyocytes. However, as proliferation and (terminal) differentiation of cardiomyocytes are mutually exclusive processes, their permanent immortalization causes loss of electrical and mechanical functions. We therefore aimed at developing conditionally immortalized atrial myocyte (iAM) lines allowing toggling between proliferative and contractile phenotypes by a single-component change in culture medium composition...
June 18, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29915331/oak-genome-reveals-facets-of-long-lifespan
#6
Christophe Plomion, Jean-Marc Aury, Joëlle Amselem, Thibault Leroy, Florent Murat, Sébastien Duplessis, Sébastien Faye, Nicolas Francillonne, Karine Labadie, Grégoire Le Provost, Isabelle Lesur, Jérôme Bartholomé, Patricia Faivre-Rampant, Annegret Kohler, Jean-Charles Leplé, Nathalie Chantret, Jun Chen, Anne Diévart, Tina Alaeitabar, Valérie Barbe, Caroline Belser, Hélène Bergès, Catherine Bodénès, Marie-Béatrice Bogeat-Triboulot, Marie-Lara Bouffaud, Benjamin Brachi, Emilie Chancerel, David Cohen, Arnaud Couloux, Corinne Da Silva, Carole Dossat, François Ehrenmann, Christine Gaspin, Jacqueline Grima-Pettenati, Erwan Guichoux, Arnaud Hecker, Sylvie Herrmann, Philippe Hugueney, Irène Hummel, Christophe Klopp, Céline Lalanne, Martin Lascoux, Eric Lasserre, Arnaud Lemainque, Marie-Laure Desprez-Loustau, Isabelle Luyten, Mohammed-Amin Madoui, Sophie Mangenot, Clémence Marchal, Florian Maumus, Jonathan Mercier, Célia Michotey, Olivier Panaud, Nathalie Picault, Nicolas Rouhier, Olivier Rué, Camille Rustenholz, Franck Salin, Marçal Soler, Mika Tarkka, Amandine Velt, Amy E Zanne, Francis Martin, Patrick Wincker, Hadi Quesneville, Antoine Kremer, Jérôme Salse
Oaks are an important part of our natural and cultural heritage. Not only are they ubiquitous in our most common landscapes 1 but they have also supplied human societies with invaluable services, including food and shelter, since prehistoric times 2 . With 450 species spread throughout Asia, Europe and America 3 , oaks constitute a critical global renewable resource. The longevity of oaks (several hundred years) probably underlies their emblematic cultural and historical importance. Such long-lived sessile organisms must persist in the face of a wide range of abiotic and biotic threats over their lifespans...
June 18, 2018: Nature Plants
https://www.readbyqxmd.com/read/29915260/differential-antiviral-immunity-to-japanese-encephalitis-virus-in-developing-cortical-organoids
#7
Boya Zhang, Yangzhige He, Yanpeng Xu, Fan Mo, Tingwei Mi, Qing Sunny Shen, Chunfeng Li, Yali Li, Jing Liu, Yihui Wu, Guilai Chen, Wenliang Zhu, Chengfeng Qin, Baoyang Hu, Guomin Zhou
Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) poses a serious threat to the world's public health yet without a cure. Certain JEV-infected neural cells express a subset of previously identified intrinsic antiviral interferon stimulated genes (ISGs), indicating brain cells retain autonomous antiviral immunity. However, whether this happens in composited brain remains unclear. Human pluripotent stem cell (hPSC)-derived organoids can model disorders caused by human endemic pathogens such as Zika virus, which may potentially address this question and facilitate the discovery of a cure for JE...
June 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29915216/pharmacokinetics-of-fludarabine-and-its-association-with-clinical-outcomes-in-paediatric-haematopoietic-stem-cell-transplantation-patients
#8
Hyewon Chung, Kyung Taek Hong, Ji Won Lee, Su-Jin Rhee, Seokuee Kim, Seo Hyun Yoon, Kyung-Sang Yu, Hyoung Jin Kang
Fludarabine is used as a common component of conditioning regimens for haematopoietic stem cell transplantation (HSCT). However, knowledge regarding the pharmacokinetic characteristics of once-daily fludarabine dosing in children is limited. This study investigated the pharmacokinetics of fludarabine and evaluated its associations with clinical outcomes in paediatric patients. A total of 802 blood samples obtained from 43 paediatric patients who underwent HSCT were included in a population pharmacokinetic analysis using non-linear mixed-effects modelling...
June 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29913643/human-inducible-pluripotent-stem-cell-derived-sensory-neurons-express-multiple-functional-ion-channels-and-gpcrs
#9
M Saarnilehto, M Pekkanen-Mattila, K Aalto-Setälä, O Silvennoinen, A Koivisto
Aims Aim of the study was to characterize functional ion channel and GPCR responses by using selective pharmacological tools and intracellular calcium imaging from human inducible pluripotent stem cell-derived sensory neurons. Methods Sensory neurons were generated from human keratinocytes that were reprogrammed to inducible pluripotent stem cells by using standard Yamanaka factors. Inducible pluripotent stem cells were differentiated into sensory neurons by using 2 differentiation protocols (small molecule and PA6 co-culture)...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29912864/evolutionary-dynamics-of-paroxysmal-nocturnal-hemoglobinuria
#10
Nathaniel Mon Père, Tom Lenaerts, Jorge M Pacheco, David Dingli
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder characterized by hemolysis and a high risk of thrombosis, that is due to a deficiency in several cell surface proteins that prevent complement activation. Its origin has been traced to a somatic mutation in the PIG-A gene within hematopoietic stem cells (HSC). However, to date the question of how this mutant clone expands in size to contribute significantly to hematopoiesis remains under debate. One hypothesis posits the existence of a selective advantage of PIG-A mutated cells due to an immune mediated attack on normal HSC, but the evidence supporting this hypothesis is inconclusive...
June 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29911897/per-and-polyfluoroalkyl-substances-impact-human-spermatogenesis-in-a-stem-cell-derived-model
#11
Alyse N Steves, Adam Turry, Brittany Gill, Danielle Clarkson-Townsend, Joshua M Bradner, Ian Bachli, W Michael Caudle, Gary W Miller, Anthony W S Chan, Charles A Easley
Per- and polyfluoroalkyl substances (PFASs) represent a highly ubiquitous group of synthetic chemicals used in products ranging from water and oil repellents and lubricants to firefighting foam. These substances can enter and accumulate in multiple tissue matrices in up to 100% of people assessed. Though animal models strongly identify these compounds as male reproductive toxicants, with exposed rodents experiencing declines in sperm count, alterations in hormones, and DNA damage in spermatids, among other adverse outcomes, human studies report conflicting conclusions as to the reproductive toxicity of these chemicals...
June 18, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29911470/endothelial-cells-are-critical-regulators-of-iron-transport-in-a-model-of-the-human-blood-brain-barrier
#12
Brian Chiou, Emma H Neal, Aaron B Bowman, Ethan S Lippmann, Ian A Simpson, James R Connor
Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29910804/targeting-inflammatory-t-helper-cells-via-retinoic-acid-related-orphan-receptor-gamma-t-is-ineffective-to-prevent-allo-response-driven-colitis
#13
Vera Buchele, Benjamin Abendroth, Maike Büttner-Herold, Tina Vogler, Johanna Rothamer, Sakhila Ghimire, Evelyn Ullrich, Ernst Holler, Markus F Neurath, Kai Hildner
Intestinal graft-versus-host disease (GvHD) is a life-threatening, inflammatory donor T cell-mediated complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the light of the reported efficacy of interleukin-23 (IL-23)-blockade to mitigate syngeneic intestinal inflammation in inflammatory bowel disease patients, targeting IL-23 and thereby interleukin-17a (IL-17a) producing T helper (Th17) cells as the T cell subset assumed to be mostly regulated by IL-23, has emerged as a putatively general concept to harness immune-mediated mucosal inflammation irrespective of the underlying trigger...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910711/functional-consequences-of-the-postnatal-switch-from-neonatal-to-mutant-adult-glycine-receptor-%C3%AE-1-subunits-in-the-shaky-mouse-model-of-startle-disease
#14
Natascha Schaefer, Fang Zheng, Johannes van Brederode, Alexandra Berger, Sophie Leacock, Hiromi Hirata, Christopher J Paige, Robert J Harvey, Christian Alzheimer, Carmen Villmann
Mutations in GlyR α1 or β subunit genes in humans and rodents lead to severe startle disease characterized by rigidity, massive stiffness and excessive startle responses upon unexpected tactile or acoustic stimuli. The recently characterized startle disease mouse mutant shaky carries a missense mutation (Q177K) in the β8-β9 loop within the large extracellular N-terminal domain of the GlyR α1 subunit. This results in a disrupted hydrogen bond network around K177 and faster GlyR decay times. Symptoms in mice start at postnatal day 14 and increase until premature death of homozygous shaky mice around 4-6 weeks after birth...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29910127/human-clinical-grade-parthenogenetic-esc-derived-dopaminergic-neurons-recover-locomotive-defects-of-nonhuman-primate-models-of-parkinson-s-disease
#15
Yu-Kai Wang, Wan-Wan Zhu, Meng-Hua Wu, Yi-Hui Wu, Zheng-Xin Liu, Ling-Min Liang, Chao Sheng, Jie Hao, Liu Wang, Wei Li, Qi Zhou, Bao-Yang Hu
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model...
June 7, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29908880/microphysiological-systems-meet-hipsc-technology-new-tools-for-disease-modeling-of-liver-infections-in-basic-research-and-drug-development
#16
Martin Raasch, Enrico Fritsche, Andreas Kurtz, Michael Bauer, Alexander S Mosig
Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC)...
June 14, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29907361/mesenchymal-stem-cell-expression-of-interleukin-35-protects-against-ulcerative-colitis-by-suppressing-mucosal-immune-responses
#17
Yongjia Yan, Na Zhao, Xianghui He, Hao Guo, Zhixiang Zhang, Tong Liu
BACKGROUND: Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs). METHODS: We used a dextran sulfate sodium (DSS)-induced colitis mice model and treated them with IL-35-MSCs, MSCs or saline. The body weight was recorded daily and inflammatory processes were determined...
June 12, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29906246/o-glycosylation-mediated-signaling-circuit-drives-metastatic-castration-resistant-prostate-cancer
#18
Sheue-Fen Tzeng, Chin-Hsien Tsai, Tai-Kuang Chao, Yu-Ching Chou, Yu-Chih Yang, Mong-Hsun Tsai, Tai-Lung Cha, Pei-Wen Hsiao
Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29905812/defective-cholesterol-metabolism-in-haematopoietic-stem-cells-promotes-monocyte-driven-atherosclerosis-in-rheumatoid-arthritis
#19
Dragana Dragoljevic, Michael J Kraakman, Prabhakara R Nagareddy, Devi Ngo, Waled Shihata, Helene L Kammoun, Alexandra Whillas, Man Kit Sam Lee, Annas Al-Sharea, Gerard Pernes, Michelle C Flynn, Graeme I Lancaster, Mark A Febbraio, Jaye Chin-Dusting, Beatriz Y Hanaoka, Ian P Wicks, Andrew J Murphy
Aim: Rheumatoid arthritis (RA) is associated with an approximately two-fold elevated risk of cardiovascular (CV)-related mortality. Patients with RA present with systemic inflammation including raised circulating myeloid cells, but fail to display traditional CV risk-factors, particularly dyslipidaemia. We aimed to explore if increased circulating myeloid cells is associated with impaired atherosclerotic lesion regression or altered progression in RA. Methods and results: Using flow cytometry, we noted prominent monocytosis, neutrophilia, and thrombocytosis in two mouse models of RA...
June 14, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29904927/mesenchymal-stromal-cells-from-amniotic-fluid-are-less-prone-to-senescence-compared-to-those-obtained-from-bone-marrow-an-in-vitro-study
#20
Nicola Alessio, Caterina Pipino, Domitilla Mandatori, Pamela Di Tomo, Angela Ferone, Marco Marchiso, Mariarosa A B Melone, Gianfranco Peluso, Assunta Pandolfi, Umberto Galderisi
Mesenchymal stromal cells (MSCs) are considered to be an excellent source in regenerative medicine. They contain several cell subtypes, including multipotent stem cells. MSCs are of particular interest as they are currently being tested using cell and gene therapies for a number of human diseases. They represent a rare population in tissues; for this reason, they require, before being transplanted, an in vitro amplification. This process may induce replicative senescence, thus affecting differentiation and proliferative capacities...
June 15, 2018: Journal of Cellular Physiology
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