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https://www.readbyqxmd.com/read/28634147/csahi-study-2-validation-of-multi-electrode-array-systems-mea60-2100-for-prediction-of-drug-induced-proarrhythmia-using-human-ips-cell-derived-cardiomyocytes-assessment-of-reference-compounds-and-comparison-with-non-clinical-studies-and-clinical-information
#1
Yumiko Nozaki, Yayoi Honda, Hitoshi Watanabe, Shota Saiki, Kiyotaka Koyabu, Tetsuji Itoh, Chiho Nagasawa, Chiaki Nakamori, Chiaki Nakayama, Hiroshi Iwasaki, Shinobu Suzuki, Kohji Tanaka, Etsushi Takahashi, Kaori Miyamoto, Kaoru Morimura, Atsuhiro Yamanishi, Hiroko Endo, Junko Shinozaki, Hisashi Nogawa, Tadahiro Shinozawa, Fumiyo Saito, Takeshi Kunimatsu
With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period...
June 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28622076/human-ips-derived-endothelial-cells-for-3d-microphysiological-systems
#2
Yosuke K Kurokawa, Rose T Yin, Michael R Shang, Venktesh S Shirure, Monica L Moya, Steven C George
Microphysiological systems, or "organ-on-a-chip", platforms, aim to recapitulate in vivo physiology using small-scale in vitro tissue models of human physiology. While significant efforts have been made to create vascularized tissues, most reports utilize primary endothelial cells which hinder reproducibility. Here we report the use of human induced pluripotent stem cell-derived endothelial cells (iPS-EC) in developing 3D microvascular networks. We established a CDH5-mCherry reporter iPS cell line, which expresses the vascular endothelial (VE)-cadherin fused to mCherry...
June 16, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28618360/the-distribution-of-phosphorus-and-its-transformations-during-batch-growth-of-synechocystis
#3
Yun Zhou, Binh T Nguyen, Chen Zhou, Levi Straka, YenJung Sean Lai, Siqing Xia, Bruce E Rittmann
Phosphorus (P) is an essential nutrient that affects the growth and metabolism of microalgal biomass. Despite the obvious importance of P, the dynamics of how it is taken up and distributed in microalgae are largely undefined. In this study, we tracked the fate of P during batch growth of the cyanobacterium Synechocystis sp. PCC 6803. We determined the distribution of P in intracellular polymeric substances (IPS), extracellular polymeric substances (EPS), and soluble microbial products (SMP) for three initial ortho-phosphate concentrations...
June 9, 2017: Water Research
https://www.readbyqxmd.com/read/28594288/in-vitro-maturation-of-human-ips-derived-neuroepithelial-cells-influences-transplant-survival-in-the-stroke-injured-rat-brain
#4
Samantha L Payne, Priya N Anandakumaran, Balazs V Varga, Cindi M Morshead, Andras Nagy, Molly S Shoichet
Stem cell transplantation is a promising strategy for brain tissue regeneration; yet, despite some success, cell survival following transplantation remains low. Here we demonstrate that cell viability is enhanced by control over maturation of neuronal precursor cells, which are delivered in an injectable blend of hyaluronan (HA) and methylcellulose (MC) (HAMC). We selected three subpopulations of human neuronal precursor cells derived from a cortically-specified neuroepithelial stem cell (cNESC) population based on differences in expression of multipotent and neuron-specific proteins: early, mid-, and late-differentiated neurons...
June 8, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28588295/cell-fiber-based-three-dimensional-culture-system-for-highly-efficient-expansion-of-human-induced-pluripotent-stem-cells
#5
Kazuhiro Ikeda, Shogo Nagata, Teru Okitsu, Shoji Takeuchi
Human pluripotent stem cells are a potentially powerful cellular resource for application in regenerative medicine. Because such applications require large numbers of human pluripotent stem cell-derived cells, a scalable culture system of human pluripotent stem cell needs to be developed. Several suspension culture systems for human pluripotent stem cell expansion exist; however, it is difficult to control the thickness of cell aggregations in these systems, leading to increased cell death likely caused by limited diffusion of gases and nutrients into the aggregations...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578413/dna-methylation-in-schizophrenia-in-different-patient-derived-cell-types
#6
Alejandra M Vitale, Nicholas A Matigian, Alexandre S Cristino, Katia Nones, Sugandha Ravishankar, Bernadette Bellette, Yongjun Fan, Stephen A Wood, Ernst Wolvetang, Alan Mackay-Sim
DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a "ground state" upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences...
January 23, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28558641/high-incidence-of-infections-in-hiv-positive-patients-treated-for-lymphoproliferative-disorders
#7
A Calcagno, A Lucchini, D Caracciolo, R Balbiano, M Bracchi, F Sordella, G Gregori, F Lipani, S Audagnotto, M Chiriotto, G Cavaglià, V Ghisetti, G Di Perri, S Bonora
BACKGROUND: Lymphoproliferative disorders are frequently diagnosed in HIV-positive patients and severe infections may occur during antineoplastic treatments: the incidence and impact of such events are not well-characterized. OBJECTIVE: To describe the occurrence and mortality of incident infections in HIV-positive individuals treated for lymphoproliferative disorders. METHODS: A retrospective study in HIV-positive adults with lymphoproliferative disorders (2000-2012) who were hospitalised to receive antineoplastic chemotherapy; as well as antimicrobial prophylaxis with alternate day co-trimoxazole (800/160 mg)...
May 30, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28552235/reprogramming-of-somatic-cells-ips-and-in-cells
#8
Vania Broccoli
Limited access to human neurons has posed a significant barrier to progress in biological and preclinical studies of the human nervous system. The advent of cell reprogramming technologies has widely disclosed unprecedented opportunities to generate renewable sources of human neural cells for disease modeling, drug discovery, and cell therapeutics. Both somatic reprogramming into induced pluripotent stem cells (iPSCs) and directly induced Neurons (iNeurons) rely on transcription factor-based cellular conversion processes...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552230/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-kyoto-trial
#9
Jun Takahashi
Concerted efforts are realizing cell-based therapy for Parkinson's disease (PD). In this chapter, I describe efforts at the Center for iPS Cell Research and Application (CiRA), Kyoto University. These efforts use induced pluripotent stem cells (iPSCs) as donor cells. The iPSCs were established as human leukocyte antigen homozygous at CiRA and are intended for allogeneic transplantation. Our manufacturing protocol includes a feeder-free cell culture with laminin fragment LM511-E8 and the sorting of CORIN(+) cells...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28546127/new-genes-for-accurate-normalization-of-qrt-pcr-results-in-study-of-ips-and-ips-derived-cells
#10
A S Artyukhov, E B Dashinimaev, V O Tsvetkov, A P Bolshakov, E V Konovalova, S N Kolbaev, E A Vorotelyak, A V Vasiliev
iPSC-derived cells (from induced pluripotent stem cells) are a useful source that provide a powerful and widely accepted tool for the study of various types of human cells in vitro. Indeed, iPSC-derived cells from patients with hereditary diseases have been shown to reproduce the hallmarks of these diseases in vitro, phenotypes that can then also be manipulated in vitro. Quantitative reverse transcription PCR (qRT-PCR) is often used to characterize the progress of iPSC differentiation, validate mature cell types and to determine levels of pathological markers...
May 22, 2017: Gene
https://www.readbyqxmd.com/read/28541280/a-quantitative-csmart-assay-for-noninvasive-prenatal-screening-of-autosomal-recessive-nonsyndromic-hearing-loss-caused-by-gjb2-and-slc26a4-mutations
#11
Mingyu Han, Zhifeng Li, Wenlu Wang, Shasha Huang, Yanping Lu, Zhiying Gao, Longxia Wang, Dongyang Kang, Linwei Li, Yiqian Liu, Mengnan Xu, David S Cram, Pu Dai
PurposeThe aim of this study was to assess the performance of a noninvasive prenatal screening (NIPS) assay for accurate fetal genotyping of pregnancies at genetic risk for autosomal recessive nonsyndromic hearing loss (ARNSHL).MethodsA total of 80 pregnant couples carrying known mutations in either the GJB2 or SLC26A4 genes associated with a risk for ARNSHL were recruited to the study. Fetal amniocyte samples were genotyped by invasive prenatal screening (IPS), whereas the cell-free fetal DNA present in maternal plasma samples was genotyped using a novel NIPS method based on circulating single-molecule amplification and resequencing technology (cSMART)...
May 25, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28539639/the-absence-of-interferon-%C3%AE-promotor-stimulator-1-ips-1-predisposes-to-bronchiolitis-and-asthma-like-pathology-in-response-to-pneumoviral-infection-in-mice
#12
Jennifer Simpson, Jason P Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B Werder, Kirsten Spann, Simon Phipps
Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539554/investigation-of-the-pathogenesis-of-autoimmune-diseases-by-ips-cells
#13
Bunki Natsumoto, Hirofumi Shoda, Keishi Fujio, Makoto Otsu, Kazuhiko Yamamoto
  The pluripotent stem cells have a self-renewal ability and can be differentiated into theoretically all of cell types. The induced pluripotent stem (iPS) cells overcame the ethical problems of the human embryonic stem (ES) cell, and enable pathologic analysis of intractable diseases and drug discovery. The in vitro disease model using disease-specific iPS cells enables repeated analyses of human cells without influence of environment factors. Even though autoimmune diseases are polygenic diseases, autoimmune disease-specific iPS cells are thought to be a promising tool for analyzing the pathogenesis of the diseases and drug discovery in future...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28530648/mechanism-of-human-somatic-reprogramming-to-ips-cell
#14
Rika Teshigawara, Junkwon Cho, Masahiro Kameda, Takashi Tada
Somatic reprogramming to induced pluripotent stem cells (iPSC) was realized in the year 2006 in mice, and in 2007 in humans, by transiently forced expression of a combination of exogenous transcription factors. Human and mouse iPSCs are distinctly reprogrammed into a 'primed' and a 'naïve' state, respectively. In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies...
May 22, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28529336/stem-cells-the-different-flavours-of-ips-cells
#15
Katharine H Wrighton
No abstract text is available yet for this article.
July 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28526755/the-matrix-protein-tiggrin-regulates-plasmatocyte-maturation-in-drosophila-larva
#16
Chen U Zhang, Ken M Cadigan
The lymph gland (LG) is a major source of hematopoiesis during Drosophila development. In this tissue, prohemocytes differentiate into multiple lineages including macrophage-like plasmatocytes, which comprise the vast majority of mature hemocytes. Previous studies have uncovered genetic pathways that regulate prohemocyte maintenance and some cell fate choices between hemocyte lineages. However, less is known about how the plasmatocyte pool of the LG is established and matures. Here we report that Tiggrin, a matrix protein expressed in the LG, is a specific regulator of plasmatocyte maturation...
May 19, 2017: Development
https://www.readbyqxmd.com/read/28494936/functional-analysis-of-dendritic-cells-generated-from-t-ipscs-from-cd4-t-cell-clones-of-sj%C3%A3-gren-s-syndrome
#17
Mana Iizuka-Koga, Hiromitsu Asashima, Miki Ando, Chen-Yi Lai, Shinji Mochizuki, Mahito Nakanishi, Toshinobu Nishimura, Hiroto Tsuboi, Tomoya Hirota, Hiroyuki Takahashi, Isao Matsumoto, Makoto Otsu, Takayuki Sumida
Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs)...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28491099/induction-of-pluripotent-stem-cells-from-a-manifesting-carrier-of-duchenne-muscular-dystrophy-and-characterization-of-their-x-inactivation-status
#18
Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu-Ichi Goto, Shin'ichi Takeda
Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28476334/novel-spliced-variants-of-oct4-oct4c-and-oct4c1-with-distinct-expression-patterns-and-functions-in-pluripotent-and-tumor-cell-lines
#19
Mahshid Malakootian, Fatemeh Mirzadeh Azad, Parisa Naeli, Mohammad Pakzad, Youssef Fouani, Elham Taheri Bajgan, Hossein Baharvand, Seyed Javad Mowla
OCT4 is a major regulator of pluripotency which has several spliced variants and expressed pseudogenes. Here, we are reporting the existence of two additional novel spliced variants of OCT4, OCT4C and OCT4C1, which lack Exon1 (E1) but start at a novel exon (E0) located ∼14kb upstream of E2. OCT4C/C1 is highly expressed in ES and iPS cells, and their expression was sharply turned off, upon the induction of neural differentiation. The long non-coding RNA (lncRNA) PSORS1C3, is located ∼9kb downstream of the E0 of OCT4C/C1...
April 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28473859/myogenic-differentiation-from-myogenin-mutated-human-ips-cells-by-crispr-cas9
#20
Koki Higashioka, Noriko Koizumi, Hidetoshi Sakurai, Chie Sotozono, Takahiko Sato
It is well known that myogenic regulatory factors encoded by the Myod1 family of genes have pivotal roles in myogenesis, with partially overlapping functions, as demonstrated for the mouse embryo. Myogenin-mutant mice, however, exhibit severe myogenic defects without compensation by other myogenic factors. MYOGENIN might be expected to have an analogous function in human myogenic cells. To verify this hypothesis, we generated MYOGENIN-mutated human iPS cells by using CRISPR/Cas9 genome-editing technology. Our results suggest that MYOD1-independent or MYOD1-dependent mechanisms can compensate for the loss of MYOGENIN and that these mechanisms are likely to be crucial for regulating skeletal muscle differentiation and formation...
2017: Stem Cells International
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