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https://www.readbyqxmd.com/read/28516002/transplantation-of-human-embryonic-stem-cell-derived-retinal-cells-into-the-subretinal-space-of-a-non-human-primate
#1
Jennifer R Chao, Deepak A Lamba, Todd R Klesert, Anna La Torre, Akina Hoshino, Russell J Taylor, Anu Jayabalu, Abbi L Engel, Thomas H Khuu, Ruikang K Wang, Maureen Neitz, Jay Neitz, Thomas A Reh
PURPOSE: Previous studies have demonstrated the ability of retinal cells derived from human embryonic stem cells (hESCs) to survive, integrate into the host retina, and mediate light responses in murine mouse models. Our aim is to determine whether these cells can also survive and integrate into the retina of a nonhuman primate, Saimiri sciureus, following transplantation into the subretinal space. METHODS: hESCs were differentiated toward retinal neuronal fates using our previously published technique and cultured for 60 to 70 days...
May 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28506532/accreditation-of-biosafe-clinical-grade-human-embryonic-stem-cells-according-to-chinese-regulations
#2
Qi Gu, Juan Wang, Lei Wang, Zheng-Xin Liu, Wan-Wan Zhu, Yuan-Qing Tan, Wei-Fang Han, Jun Wu, Chun-Jing Feng, Jin-Hui Fang, Lei Liu, Liu Wang, Wei Li, Xiao-Yang Zhao, Bao-Yang Hu, Jie Hao, Qi Zhou
Human embryonic stem cells (hESCs) are promising in regenerative medicine. Although several hESC-based clinical trials are under way, a widely accepted standard of clinical-grade cells remains obscure. To attain a completely xeno-free clinical-grade cell line, the system must be free of xenogenic components, the cells must have a comprehensive set of functions, and good manufacturing practice conditions must be used. In this study, following these criteria, we successfully derived two hESC lines, which were thereby considered "clinical-grade embryonic stem cells"...
May 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#3
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28487297/mechanisms-in-endocrinology-towards-the-clinical-translation-of-stem-cell-therapy-for-type-1-diabetes
#4
Daniel Espes, Joey Lau Börjesson, Per-Ola Carlsson
Insulin producing cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) have for long been a promising, but elusive treatment far from clinical translation into type 1 diabetes therapy. However, the field is now on the verge of moving such insulin-producing cells into clinical trials. Although stem cell therapies provide great opportunities, there are also potential risks such as teratoma formation associated with the treatment. Many considerations are needed on how to proceed with clinical translation, including whether to use hESCs or iPSCs, and whether encapsulation of tissue will be needed...
May 9, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28477133/dna-damage-response-in-human-stem-cells-and-neural-descendants
#5
Jason M Beckta, Bret R Adams, Kristoffer Valerie
Glial cells are crucial for the normal function of neurons and are intricately involved in the pathogenesis of neurodegenerative diseases as well as neurologic malignancies. A deeper understanding of the mechanisms by which glial cells influence the development of such pathologies will undoubtedly lead to new and improved therapeutic approaches. Commercially available human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), both of which can be differentiated into neural progenitors (NPs) and various neural cell lineages, have become widely used as sources for producing normal human central nervous system (CNS) cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28476540/epigenetic-and-transcriptional-modulation-of-wdr5-a-chromatin-remodeling-protein-in-huntington-s-disease-human-induced-pluripotent-stem-cell-hipsc-model
#6
Simona Baronchelli, Alberto La Spada, Aikaterini Ntai, Andrea Barbieri, Paola Conforti, Gloria Saccani Jotti, Serena Redaelli, Angela Bentivegna, Pasquale De Blasio, Ida Biunno
DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs. Subsequently, we focused on the methylation differences in a subcluster of genes related to Jumonji Domain Containing 3 (JMJD3), a demethylase that epigenetically regulates neuronal differentiation and activates neuronal progenitor associated genes, which are indispensable for neuronal fate acquisition...
May 2, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28475175/nucleosome-eviction-along-with-h3k9ac-deposition-enhances-sox2-binding-during-human-neuroectodermal-commitment
#7
Yanhua Du, Zhenping Liu, Xinkai Cao, Xiaolong Chen, Zhenyu Chen, Xiaobai Zhang, Xiaoqing Zhang, Cizhong Jiang
Neuroectoderm is an important neural precursor. However, chromatin remodeling and its epigenetic regulatory roles during the differentiation of human neuroectodermal cells (hNECs) from human embryonic stem cells (hESCs) remain largely unexplored. Here, we obtained hNECs through directed differentiation from hESCs, and determined chromatin states in the two cell types. Upon differentiation, H2A.Z-mediated nucleosome depletion leads to an open chromatin structure in promoters and upregulates expression of neuroectodermal genes...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28474621/feeder-basic-fibroblast-growth-factor-free-culture-of-human-embryonic-stem-cells-role-of-conditioned-medium-from-immortalized-human-feeders
#8
Pooja Teotia, Shilpa Sharma, Balram Airan, Sujata Mohanty
BACKGROUND & OBJECTIVES: Human embryonic stem cell (hESC) lines are commonly maintained on inactivated feeder cells, in the medium supplemented with basic fibroblast growth factor (bFGF). However, limited availability of feeder cells in culture, and the high cost of growth factors limit their use in scalable expansion of hESC cultures for clinical application. Here, we describe an efficient and cost-effective feeder and bFGF-free culture of hESCs using conditioned medium (CM) from immortalized feeder cells...
December 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28474496/an-arduous-journey-from-human-pluripotent-stem-cells-to-functional-pancreatic-%C3%AE-cells
#9
REVIEW
Larry Sai Weng Loo, Hwee Hui Lau, Joanita Binte Jasmen, Chang Siang Lim, Adrian Kee Keong Teo
Type 1 and type 2 diabetes are caused by either a destruction or decrease in the number of functional insulin-producing β-cells, respectively. Therefore, the generation of functional β-cells from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), collectively known as human pluripotent stem cells (hPSCs), for potential cell replacement therapy and disease modeling is an intensely investigated area. Recent scientific breakthroughs enabled derivation of large quantities of human pancreatic β-like cells in vitro although with varied glucose-stimulated insulin secretion kinetics...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28466868/a-sequential-emt-met-mechanism-drives-the-differentiation-of-human-embryonic-stem-cells-towards-hepatocytes
#10
Qiuhong Li, Andrew P Hutchins, Yong Chen, Shengbiao Li, Yongli Shan, Baojian Liao, Dejin Zheng, Xi Shi, Yinxiong Li, Wai-Yee Chan, Guangjin Pan, Shicheng Wei, Xiaodong Shu, Duanqing Pei
Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28450050/transgenic-human-embryonic-stem-cells-overexpressing-fgf2-stimulate-neuroprotection-following-spinal-cord-ventral-root-avulsion
#11
Marta Rocha Araújo, Sergiy Kyrylenko, Aline Barroso Spejo, Mateus Vidigal Castro, Rui Seabra Ferreira Junior, Benedito Barraviera, Alexandre Leite Rodrigues Oliveira
Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold...
April 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28435121/proteome-analysis-of-human-embryonic-stem-cells-organelles
#12
Faezeh Shekari, Hossein Nezari, Mehran Rezaei Larijani, Chia-Li Han, Hossein Baharvand, Yu-Ju Chen, Ghasem Hosseini Salekdeh
As the functions of proteins are associated with their cellular localization, the comprehensive sub-cellular proteome knowledge of human embryonic stem cells (hESCs) is indispensable for ensuring a therapeutic effect. Here, we have utilized a sub-cellular proteomics approach to analyze the localization of proteins in the nucleus, mitochondria, crude membrane, cytoplasm, heavy and light microsomes. Out of 2002 reproducibly identified proteins, we detected 762 proteins in a single organelle whereas 160 proteins were found in all sub-cellular fractions...
April 20, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28433654/high-molecular-weight-fgf2-isoforms-demonstrate-canonical-receptor-mediated-activity-and-support-human-embryonic-stem-cell-self-renewal
#13
Denis Kole, Alexandra Grella, David Dolivo, Lucia Shumaker, William Hermans, Tanja Dominko
Basic fibroblast growth factor (FGF2) is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006), and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011). A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18kDa low molecular weight (LMW) isoform and four larger high molecular weight (HMW) isoforms (Arese et al...
April 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28433627/docosahexaenoic-acid-promotes-differentiation-of-photoreceptor-cells-in-three-dimensional-neural-retinas
#14
Eisuke Arai, Vipul M Parmar, Bhubanananda Sahu, Lindsay Perusek, Tanu Parmar, Akiko Maeda
Retinal tissues generated from human pluripotent stem cells can be an excellent tool for investigating pathogenesis of retinal diseases and developing new pharmacologic therapies. Moreover, patient derived retinal tissues could allow for retinal transplantation therapy for degenerative retinal diseases. However, obtaining retinal tissues with matured photoreceptor outer segments, which are essential for photoreceptor functions, is currently challenging. Here we investigated the effects of docosahexaenoic acid (DHA) for maturation of photoreceptor outer segments at the late stage and visual chromophore analog, 9-cis-retinal for the early stage of differentiation to three-dimensional (3D)-retinal tissues from human embryonic stem cells (hESCs), respectively...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28433626/thrombin-impairs-human-endometrial-endothelial-angiogenesis-implications-for-progestin-only-contraceptive-induced-abnormal-uterine-bleeding
#15
John P Shapiro, Ozlem Guzeloglu-Kayisli, Umit A Kayisli, Nihan Semerci, S Joseph Huang, Sefa Arlier, Kellie Larsen, Paolo Fadda, Frederick Schatz, Charles J Lockwood
OBJECTIVE: Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by pro-thrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis...
April 19, 2017: Contraception
https://www.readbyqxmd.com/read/28430877/the-accessible-chromatin-landscape-during-conversion-of-human-embryonic-stem-cells-to-trophoblast-by-bmp4
#16
Yajun Liu, Dewu Ding, Hongde Liu, Xiao Sun
Human embryonic stem cells (hESC) exposed to the growth factor bone morphogenic protein 4 (BMP4) in the absence of FGF2 have been used as a model to study the development of placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. In this study, we used the public available chromatin accessibility data of hESC H1 cells and BMP4-induced trophoblast (TB)cell lines to identify DNase I hypersensitive sites (DHSs) in the two cell lines, as well as the transcription factor binding sites within the DHSs...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28429706/direct-comparison-of-distinct-naive-pluripotent-states-in-human-embryonic-stem-cells
#17
S Warrier, M Van der Jeught, G Duggal, L Tilleman, E Sutherland, J Taelman, M Popovic, S Lierman, S Chuva De Sousa Lopes, A Van Soom, L Peelman, F Van Nieuwerburgh, D I M De Coninck, B Menten, P Mestdagh, J Van de Sompele, D Deforce, P De Sutter, B Heindryckx
Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive or primed pluripotent state. Here we show the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state within 5-6 days in naive conversion media (NCM-MEF), 6-10 days in naive human stem cell media (NHSM-MEF) and 14-20 days using the reverse-toggle protocol (RT-MEF). We further observe enhanced unbiased lineage-specific differentiation potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to differentiate towards functional cell types...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28413007/a-homozygous-keap1-knockout-human-embryonic-stem-cell-line-generated-using-crispr-cas9-mediates-gene-targeting
#18
So-Jung Kim, Omer Habib, Jin-Soo Kim, Hyo-Won Han, Soo Kyung Koo, Jung-Hyun Kim
Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28413005/generation-of-a-nrf2-homozygous-knockout-human-embryonic-stem-cell-line-using-crispr-cas9
#19
So-Jung Kim, Omer Habib, Jin-Soo Kim, Hyo-Won Han, Soo Kyung Koo, Jung-Hyun Kim
Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2) is a well-known transcription factor that regulates the expression of a large number of anti-oxidant genes in mammalian cells (J.H. Kim et al., 2014). Here, we generated a homozygous Nrf2 knockout human embryonic stem cell (hESC) line, H9Nrf2KO-A13, using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell line maintains pluripotency, differentiation potential into three germ layers, and a normal karyotype.
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28412746/kr%C3%A3-ppel-like-factor-4-klf4-regulates-the-mir-183-96-182-cluster-under-physiologic-and-pathologic-conditions
#20
Miguel F Segura, Luz Jubierre, SiDe Li, Aroa Soriano, Lisa Koetz, Avital Gaziel-Sovran, Marc Masanas, Kevin Kleffman, John F Dankert, Martin J Walsh, Eva Hernando
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post-transcriptionally control the translation and stability of target mRNAs in a sequence-dependent manner. MiRNAs are essential for key cellular processes including proliferation, differentiation, cell death and metabolism, among others. Consequently, alterations of miRNA expression contribute to developmental defects and a myriad of diseases.The expression of miRNAs can be altered by several mechanisms including gene copy number alterations, aberrant DNA methylation, defects of the miRNA processing machinery or unscheduled expression of transcription factors...
April 18, 2017: Oncotarget
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