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Induced pluripotent stem

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https://www.readbyqxmd.com/read/29656178/generation-of-3-spinocerebellar-ataxia-type-1-sca1-patient-derived-induced-pluripotent-stem-cell-lines-lumci002-a-b-and-c-and-2-unaffected-sibling-control-induced-pluripotent-stem-cell-lines-lumci003-a-and-b
#1
Ronald A M Buijsen, Sarah L Gardiner, Marga J Bouma, Linda M van der Graaf, Merel W Boogaard, Barry A Pepers, Bert Eussen, Annelies de Klein, Christian Freund, Willeke M C van Roon-Mom
Spinocerebellar ataxia type 1 (SCA1) is a hereditary neurodegenerative disease caused by a CAG repeat expansion in exon 8 of the ATXN1 gene. We generated induced pluripotent stem cells (hiPSCs) from a SCA1 patient and his non-affected sister by using non-integrating Sendai Viruses (SeV). The resulting hiPSCs are SeVfree, express pluripotency markers, display a normal karyotype, retain the mutation (length of the CAG repeat expansion in the ATXN1 gene) and are able to differentiate into the three germ layers in vitro...
April 5, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29653394/generation-of-duchenne-muscular-dystrophy-patient-specific-induced-pluripotent-stem-cell-line-lacking-exons-45-50-of-the-dystrophin-gene-iiti001-a
#2
Binyamin Eisen, Ronen Ben Jehuda, Ashley J Cuttitta, Lucy N Mekies, Irina Reiter, Sindhu Ramchandren, Michael Arad, Daniel E Michele, Ofer Binah
Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease caused by mutations in the dystrophin gene. We generated induced pluripotent stem cells (iPSCs) from a 13-year-old male patient carrying a deletion mutation of exons 45-50; iPSCs were subsequently differentiated into cardiomyocytes. iPSCs exhibit expression of the pluripotent markers (SOX2, NANOG, OCT4), differentiation capacity into the three germ layers, normal karyotype, genetic identity to the skin biopsy dermal fibroblasts and the patient-specific dystrophin mutation...
April 3, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29653250/pluripotent-stem-cell-based-therapy-for-parkinson-s-disease-current-status-and-future-prospects
#3
REVIEW
Kai-C Sonntag, Bin Song, Nayeon Lee, Jin Hyuk Jung, Young Cha, Pierre Leblanc, Carolyn Neff, Sek Won Kong, Bob S Carter, Jeffrey Schweitzer, Kwang-Soo Kim
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease...
April 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#4
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
April 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29652595/stem-cells-for-skeletal-muscle-tissue-engineering
#5
Molly N Pantellic, Lisa Marie Larkin
Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML...
March 14, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29652170/pulmonary-transplantation-of-human-ipsc-derived-macrophages-ameliorates-pulmonary-alveolar-proteinosis
#6
Christine Happle, Nico Lachmann, Mania Ackermann, Anja Mirenska, Gudrun Göhring, Kathrin Thomay, Adele Mucci, Miriam Hetzel, Torsten Glomb, Takuji Suzuki, Claudia Chalk, Silke Glage, Oliver Dittrich-Breiholz, Bruce Trapnell, Thomas Moritz, Gesine Hansen
Rationale While the transplantation of induced pluripotent stem cell (iPSC)-derived cells harbors enormous potential for the treatment of pulmonary diseases, in vivo data demonstrating clear therapeutic benefits of human iPSC-derived cells in lung disease models is missing. Objective We here tested the therapeutic potential of iPSC-derived macrophages in a humanized disease model of hereditary pulmonary alveolar proteinosis (herPAP). herPAP is caused by a genetic defect of the GM-CSF-receptor, which leads to disturbed macrophage differentiation and protein/surfactant degradation in the lungs subsequently resulting in severe respiratory insufficiency...
April 13, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29651156/efficient-differentiation-of-cardiomyocytes-and-generation-of-calcium-sensor-reporter-lines-from-nonhuman-primate-ipscs
#7
Yongshun Lin, Huimin Liu, Michael Klein, John Ostrominski, So Gun Hong, Ravi Chandra Yada, Guibin Chen, Keron Navarengom, Robin Schwartzbeck, Hong San, Zu-Xi Yu, Chengyu Liu, Kaari Linask, Jeanette Beers, Lugui Qiu, Cynthia E Dunbar, Manfred Boehm, Jizhong Zou
Nonhuman primate (NHP) models are more predictive than rodent models for developing induced pluripotent stem cell (iPSC)-based cell therapy, but robust and reproducible NHP iPSC-cardiomyocyte differentiation protocols are lacking for cardiomyopathies research. We developed a method to differentiate integration-free rhesus macaque iPSCs (RhiPSCs) into cardiomyocytes with >85% purity in 10 days, using fully chemically defined conditions. To enable visualization of intracellular calcium flux in beating cardiomyocytes, we used CRISPR/Cas9 to stably knock-in genetically encoded calcium indicators at the rhesus AAVS1 safe harbor locus...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650976/wnt-signal-activation-induces-midbrain-specification-through-direct-binding-of-the-beta-catenin-tcf4-complex-to-the-en1-promoter-in-human-pluripotent-stem-cells
#8
Ji Young Kim, Jae Souk Lee, Hyun Sub Hwang, Dongjin R Lee, Chul-Yong Park, Sung Jun Jung, Young Rang You, Dae-Sung Kim, Dong-Wook Kim
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs)...
April 13, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29648536/silencing-of-transposable-elements-may-not-be-a-major-driver-of-regulatory-evolution-in-primate-ipscs
#9
Michelle C Ward, Siming Zhao, Kaixuan Luo, Bryan J Pavlovic, Mohammad M Karimi, Matthew Stephens, Yoav Gilad
Transposable elements (TEs) comprise almost half of primate genomes and their aberrant regulation can result in deleterious effects. In pluripotent stem cells, rapidly-evolving KRAB-ZNF genes target TEs for silencing by H3K9me3. To investigate the evolution of TE silencing, we performed H3K9me3 ChIP-seq experiments in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We identified four million orthologous TEs and found the SVA and ERV families to be marked most frequently by H3K9me3...
April 12, 2018: ELife
https://www.readbyqxmd.com/read/29644628/quantitatively-characterizing-drug-induced-arrhythmic-contractile-motions-of-human-stem-cell-derived-cardiomyocytes
#10
Plansky Hoang, Nathaniel Huebsch, Shin Hyuk Bang, Brian A Siemons, Bruce R Conklin, Kevin E Healy, Zhen Ma, Sabir Jacquir
Quantification of abnormal contractile motions of cardiac tissue has been a noteworthy challenge and significant limitation in assessing and classifying the drug-induced arrhythmias (i.e. Torsades de pointes). To overcome these challenges, researchers have taken advantage of computational image processing tools to measure contractile motion from cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs). However, the amplitude and frequency analysis of contractile motion waveforms doesn't produce sufficient information to objectively classify the degree of variations between two or more sets of cardiac contractile motions...
April 12, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29643329/shared-effects-of-disc1-disruption-and-elevated-wnt-signaling-in-human-cerebral-organoids
#11
Priya Srikanth, Valentina N Lagomarsino, Christina R Muratore, Steven C Ryu, Amy He, Walter M Taylor, Constance Zhou, Marlise Arellano, Tracy L Young-Pearse
The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29642402/therapeutic-use-of-stem-cells-for-myocardial-infarction
#12
REVIEW
Mariah Madigan, Rony Atoui
Myocardial infarction is a leading cause of morbidity and mortality worldwide. Although medical and surgical treatments can significantly improve patient outcomes, no treatment currently available is able to generate new contractile tissue or reverse ischemic myocardium. Driven by the recent/novel understanding that regenerative processes do exist in the myocardium-tissue previously thought not to possess regenerative properties-the use of stem cells has emerged as a promising therapeutic approach with high expectations...
April 6, 2018: Bioengineering
https://www.readbyqxmd.com/read/29628445/the-telomerase-inhibitor-azt-enhances-differentiation-and-prevents-overgrowth-of-human-pluripotent-stem-cell-derived-neural-progenitors
#13
Yao Hu, Kai-Heng Fang, Lu-Ping Shen, Shi-Ying Cao, Fang Yuan, Yuwen Su, Min Xu, Yaoyu Chen, Yan Liu
Human pluripotent stem cell (hPSC)-based cell-replacement therapy has emerged as a promising approach for addressing numerous neurological diseases. However, hPSC transplantation has the potential to cause human cell overgrowth and cancer, which represents a major obstacle to implementing hPSC-based therapies. Inhibition of the overgrowth of transplanted cells could help reduce the risk for hPSC transplantation-induced tumorigenesis. In this study, we report that the telomerase inhibitor azidothymidine (3'-azido-3'-deoxythymidine, AZT) enhances the differentiation of cortical neurons and significantly suppresses the proliferation of hPSC-derived cortical progenitors...
April 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29627726/generation-of-wae001-a-15-a-human-embryonic-stem-cell-line-with-mir-122-doxycycline-inducible-expression
#14
Yanli Liu, Feima Wu, Dong Liu, Ruzhi Wei, Nasir Abbas, Jianhong Xia, Dongwei Li, Haiyun Wang, Yuanqi Zhuang, Dongsheng Guo, Yan Chen, Yuhang Wu, Xinrong Ke, Jiawang Tao, Fan Yang, Keyu Lai, Xiaodong Shu, Yin-Xiong Li
MiR-122 is the most abundant miRNA in the human liver accounting for 52% of the entire hepatic miRNome. Previous studies have demonstrated that miR-122 is a valuable therapeutic target for liver diseases, including viral hepatitis, fibrosis, steatosis, and hepatocarcinoma. Here, we constructed a miR-122 doxycycline-inducible expression human embryonic stem cell line WAe001-A-15 using the piggyBac transposon system. The cell line retained its pluripotency, in vitro differentiation potential, normal morphology, and karyotype...
March 23, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29626316/comparative-in-silico-profiling-of-epigenetic-modifiers-in-human-tissues
#15
Mi-Young Son, Cho-Rok Jung, Dae-Soo Kim, Hyun-Soo Cho
The technology of tissue differentiation from human pluripotent stem cells has attracted attention as a useful resource for regenerative medicine, disease modeling and drug development. Recent studies have suggested various key factors and specific culture methods to improve the successful tissue differentiation and efficient generation of human induced pluripotent stem cells. Among these methods, epigenetic regulation and epigenetic signatures are regarded as an important hurdle to overcome during reprogramming and differentiation...
April 6, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29625575/targeted-genome-engineering-in-human-induced-pluripotent-stem-cells-from-patients-with-hemophilia-b-using-the-crispr-cas9-system
#16
Cuicui Lyu, Jun Shen, Rui Wang, Haihui Gu, Jianping Zhang, Feng Xue, Xiaofan Liu, Wei Liu, Rongfeng Fu, Liyan Zhang, Huiyuan Li, Xiaobing Zhang, Tao Cheng, Renchi Yang, Lei Zhang
BACKGROUND: Replacement therapy for hemophilia remains a lifelong treatment. Only gene therapy can cure hemophilia at a fundamental level. The clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) system is a versatile and convenient genome editing tool which can be applied to gene therapy for hemophilia. METHODS: A patient's induced pluripotent stem cells (iPSCs) were generated from their peripheral blood mononuclear cells (PBMNCs) using episomal vectors...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29625481/induced-pluripotent-stem-cells-promote-retinal-ganglion-cell-survival-after-transplant
#17
Suqian Wu, Kun-Che Chang, Michael Nahmou, Jeffrey L Goldberg
Purpose: The purpose of this study was to characterize whether induced pluripotent stem cells (iPSCs) affect survival of grafted retinal ganglion cells (RGCs) after transplantation. Methods: For in vitro studies, human iPSCs were either directly cocultured with mouse RGCs or plated in hanging inserts in RGC cultures for 1 week. For ex vivo studies, RGCs and iPSCs were seeded onto the inner surface of an adult rat retina explant and cultured for 1 week. For in vivo studies, RGCs and iPSCs were intravitreally coinjected into an adult rat eye 1 week before examining retinas by explant and immunostaining...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29625185/epigenetic-modifications-in-the-embryonic-and-induced-pluripotent-stem-cells
#18
Rasoul Godini, Haider Yabr Lafta, Hossein Fallahi
Epigenetic modifications are involved in global reprogramming of the cell transcriptome. Therefore, synchronized major shifts in the expression of many genes could be achieved through epigenetic changes. The regulation of gene expression could be implemented by different epigenetic events including histone modifications, DNA methylation and chromatin remodelling. Interestingly, it has been documented that reprogramming of somatic cells to induced pluripotent stem (iPS) cells is also a typical example of epigenetic modifications...
April 4, 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29623532/genome-editing-in-induced-pluripotent-stem-cells-using-crispr-cas9
#19
REVIEW
Ronen Ben Jehuda, Yuval Shemer, Ofer Binah
The development of the reprogramming technology led to generation of induced Pluripotent Stem Cells (iPSC) from a variety of somatic cells. Ever since, fast growing knowledge of different efficient protocols enabled the differentiation of these iPSCs into different cells types utilized for disease modeling. Indeed, iPSC-derived cells have been increasingly used for investigating molecular and cellular pathophysiological mechanisms underlying inherited diseases. However, a major barrier in the field of iPSC-based disease modeling relies on discriminating between the effects of the causative mutation and the genetic background of these cells...
April 6, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29622803/simultaneous-reprogramming-and-gene-editing-of-human-fibroblasts
#20
Sara E Howden, James A Thomson, Melissa H Little
The utility of human induced pluripotent stem cells (iPSCs) is enhanced by an ability to precisely modify a chosen locus with minimal impact on the remaining genome. However, the derivation of gene-edited iPSCs typically involves multiple steps requiring lengthy culture periods and several clonal events. Here, we describe a one-step protocol for reliable generation of clonally derived gene-edited iPSC lines from human fibroblasts in the absence of drug selection or FACS enrichment. Using enhanced episomal-based reprogramming and CRISPR/Cas9 systems, gene-edited and passage-matched unmodified iPSC lines are obtained following a single electroporation of human fibroblasts...
May 2018: Nature Protocols
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