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https://www.readbyqxmd.com/read/29342186/doxorubicin-provoked-increase-of-mitotic-activity-and-concomitant-drain-of-g0-pool-in-therapy-resistant-be-2-c-neuroblastoma
#1
Isabell Hultman, Linnea Haeggblom, Ingvild Rognmo, Josefin Jansson Edqvist, Evelina Blomberg, Rouknuddin Ali, Lottie Phillips, Bengt Sandstedt, Per Kogner, Shahrzad Shirazi Fard, Lars Ährlund-Richter
In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation...
2018: PloS One
https://www.readbyqxmd.com/read/29337120/deriving-dorsal-spinal-sensory-interneurons-from-human-pluripotent-stem%C3%A2-cells
#2
Sandeep Gupta, Daniel Sivalingam, Samantha Hain, Christian Makkar, Enrique Sosa, Amander Clark, Samantha J Butler
Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29336267/stem-cells-derived-from-amniotic-fluid-a-potential-pluripotent-like-cell-source-for-cellular-therapy
#3
Thamil Selvee Ramasamy, Vithya Velaithan, Yelena Yeow, Fazlul H Sarkar
BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach that the conventional medicine cannot do. The ethical issues rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine...
January 14, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29335803/contribution-of-transposable-elements-and-distal-enhancers-to-evolution-of-human-specific-features-of-interphase-chromatin-architecture-in-embryonic-stem-cells
#4
Gennadi V Glinsky
Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs...
January 15, 2018: Chromosome Research
https://www.readbyqxmd.com/read/29333086/ethical-and-safety-issues-of-stem-cell-based-therapy
#5
REVIEW
Vladislav Volarevic, Bojana Simovic Markovic, Marina Gazdic, Ana Volarevic, Nemanja Jovicic, Nebojsa Arsenijevic, Lyle Armstrong, Valentin Djonov, Majlinda Lako, Miodrag Stojkovic
Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29330377/phenotypic-and-functional-characterization-of-peripheral-sensory-neurons-derived-from-human-embryonic-stem-cells
#6
Abdullah Jawad Alshawaf, Serena Viventi, Wanzhi Qiu, Giovanna D'Abaco, Bryony Nayagam, Michael Erlichster, Gursharan Chana, Ian Everall, Jason Ivanusic, Efstratios Skafidas, Mirella Dottori
The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes that function to relay sensory stimuli, including temperature, pressure, pain and position to the central nervous system. Our knowledge of DRG sensory neurons have been predominantly driven by animal studies and considerably less is known about the human DRG. Human embryonic stem cells (hESC) are valuable resource to help close this gap. Our previous studies reported an efficient system for deriving neural crest and DRG sensory neurons from hESC...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327467/erbb3-binding-protein-ebp1-is-a-novel-dppa4-cofactor-in-human-pluripotent-cells
#7
Priyanka Somanath, Kelly M Bush, Paul S Knoepfler
Developmental Pluripotency-Associated-4 (DPPA4) is one of the few core pluripotency genes lacking clearly defined molecular and cellular functions. Here we used a proteomics screening approach of human embryonic stem cell (hESC) nuclear extract to determine DPPA4 molecular functions through identification of novel cofactors. Unexpectedly, the signaling molecule ERBB3-binding protein 1 (EBP1) was the strongest candidate binding partner for DPPA4 in hESC. EBP1 is a growth factor signaling mediator present in two isoforms, p48 and p42...
January 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29326300/relationship-between-histone-modifications-and-transcription-factor-binding-is-protein-family-specific
#8
Beibei Xin, Remo Rohs
The very small fraction of putative binding sites (BSs) that are occupied by transcription factors (TFs) in vivo can be highly variable across different cell types. This observation has been partly attributed to changes in chromatin accessibility and histone modification (HM) patterns surrounding BSs. Previous studies focusing on BSs within DNA regulatory regions found correlations between HM patterns and TF binding specificities. However, a mechanistic understanding of TF-DNA binding specificity determinants is still not available...
January 11, 2018: Genome Research
https://www.readbyqxmd.com/read/29326135/isolation-of-human-testicular-cells-and-co-culture-with-embryonic-stem-cells
#9
Meenakshi Gaur, Cyril Ramathal, Renee A Reijo Pera, Paul J Turek, Constance M John
Our overall goal is to create a three-dimensional human cell-based testicular model for toxicological and spermatogenesis studies. Methods to purify the major somatic testicular cells, namely Leydig cells (LCs), peritubular myoid cells (PCs) and Sertoli cells (SCs), from rats, mice and guinea pigs have been reported. In humans, the isolation of populations enriched for primary LCs, PCs or SCs also have described. One objective of this study was to determine if populations of cells enriched for all three of these cell types can be isolated from testes of single human donors, and we were successful in doing so from testes of three donors...
February 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29323720/tfcp2l1-safeguards-the-maintenance-of-human-embryonic-stem-cell-self-renewal
#10
Hongwei Sun, Yu You, Mengmeng Guo, Xiaohu Wang, Yan Zhang, Shoudong Ye
Tfcp2l1 is a transcription factor critical for mouse embryonic stem cell (mESC) maintenance. However, its role in human ESCs (hESCs) remains unclear. Here, we investigated the functions of Tfcp2l1 in controlling hESC activity and showed that Tfcp2l1 is functionally important in the maintenance of hESC identity. Tfcp2l1 expression is highly enriched in hESCs and dramatically decreases upon differentiation. Forced expression of Tfcp2l1 promoted hESC self-renewal. Functional analysis of the mutant forms of Tfcp2l1 revealed that both the CP2- and SAM-like domains are indispensable for Tfcp2l1 to maintain the undifferentiated state of hESCs...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318501/function-of-fezf1-during-early-neural-differentiation-of-human-embryonic-stem-cells
#11
Xin Liu, Pei Su, Lisha Lu, Zicen Feng, Hongtao Wang, Jiaxi Zhou
The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development...
January 2, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29316243/development-of-an-alginate-array-platform-to-decouple-the-effect-of-multiparametric-perturbations-on-human-pluripotent-stem-cells-during-pancreatic-differentiation
#12
Thomas C Richardson, Shibin Mathew, Joseph E Candiello, Saik K Goh, Prashant N Kumta, Ipsita Banerjee
Human embryonic stem cells (hESC)-derived functional cells hold great promise for regenerative cell therapy. Currently approved strategies for clinical translation requires the isolation of the hESCs-derived cells in materials allowing transfer of reagents but preventing integration with the host. However, hESC fate is known to be sensitive to its local microenvironment, both chemical and physical. Given the complexity of hESC response to environmental parameters, it will be important to evaluate the cell response to multiple combinatorial perturbations...
January 5, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29315213/identification-of-transposable-elements-contributing-to-tissue-specific-expression-of-long-non-coding-rnas
#13
Takafumi Chishima, Junichi Iwakiri, Michiaki Hamada
It has been recently suggested that transposable elements (TEs) are re-used as functional elements of long non-coding RNAs (lncRNAs). This is supported by some examples such as the human endogenous retrovirus subfamily H (HERVH) elements contained within lncRNAs and expressed specifically in human embryonic stem cells (hESCs), as required to maintain hESC identity. There are at least two unanswered questions about all lncRNAs. How many TEs are re-used within lncRNAs? Are there any other TEs that affect tissue specificity of lncRNA expression? To answer these questions, we comprehensively identify TEs that are significantly related to tissue-specific expression levels of lncRNAs...
January 9, 2018: Genes
https://www.readbyqxmd.com/read/29305588/short-term-retinoic-acid-treatment-sustains-pluripotency-and-suppresses-differentiation-of-human-induced-pluripotent-stem-cells
#14
Maria Teresa De Angelis, Elvira Immacolata Parrotta, Gianluca Santamaria, Giovanni Cuda
Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) derived from blastocyst and human induced pluripotent stem cells (hiPSCs) generated from somatic cells by ectopic expression of defined transcriptional factors, have both the ability to self-renew and to differentiate into all cell types. Here we explored the two antagonistic effects of retinoic acid (RA) on hiPSCs. Although RA has been widely described as a pharmacological agent with a critical role in initiating differentiation of pluripotent stem cells, we demonstrate that short-term RA exposure not only antagonizes cell differentiation and sustains pluripotency of hiPSCs, but it also boosts and improves their properties and characteristics...
January 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29291512/generation-of-fhl2-homozygous-knockout-lines-from-human-embryonic-stem-cells-by-crispr-cas9-mediated-ablation
#15
Chia-Wei Chang, Chih-Chia Chang, Kuo-Chiang Hsia, Su-Yi Tsai
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Mutations in the FHL2 (Four and a half LIM domains protein 2) gene are associated with cardiomyopathy in patients. Here, we generated two homozygous knockout lines using CRISPR/Cas9-mediated ablation in a human embryonic stem cell (hESC) WA09 line. These knockout lines exhibit a normal karyotype without expressing FHL2 protein, while maintaining pluripotency and differentiation properties. These isogenic mutation lines will be provided as a disease model for cardiomyopathy studies and drug screening...
December 23, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29289958/regulatory-variants-of-foxg1-in-the-context-of-its-topological-domain-organisation
#16
Mana M Mehrjouy, Ana Carolina S Fonseca, Nadja Ehmke, Giorgio Paskulin, Antonio Novelli, Francesco Benedicenti, Maria Antonietta Mencarelli, Alessandra Renieri, Tiffany Busa, Chantal Missirian, Claus Hansen, Kikue Terada Abe, Carlos Eduardo Speck-Martins, Angela M Vianna-Morgante, Mads Bak, Niels Tommerup
FOXG1 syndrome is caused by FOXG1 intragenic point mutations, or by long-range position effects (LRPE) of intergenic structural variants. However, the size of the FOXG1 regulatory landscape is uncertain, because the associated topologically associating domain (TAD) in fibroblasts is split into two domains in embryonic stem cells (hESC). Indeed, it has been suggested that the pathogenetic mechanism of deletions that remove the stem-cell-specific TAD boundary may be enhancer adoption due to ectopic activity of enhancer(s) located in the distal hESC-TAD...
December 30, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29285285/ginseng-rh2-protects-endometrial-cells-from-oxygen-glucose-deprivation-re-oxygenation
#17
Xiao-Fang Tang, Hai-Yan Liu, Ling Wu, Min-Hui Li, Shu-Ping Li, Hong-Bin Xu
In this study, oxygen glucose deprivation/re-oxygenation (OGDR) was applied to cultured endometrial cells to mimic ischemic-reperfusion injuries. We also tested the potential effect of Ginseng Rh2 (GRh2) against the process. In established T-HESC human endometrial cells and primary murine endometrial cells, GRh2 largely inhibited OGDR-induced viability reduction and cell death. Remarkably, OGDR induced programmed necrosis in the endometrial cells, evidenced by cyclophilin D-p53-adenine nucleotide translocator 1 (ANT-1) mitochondrial association, mitochondrial depolarization, reactive oxygen species production, and lactate dehydrogenase release...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284013/creating-a-stem-cell-niche-in-the-inner-ear-using-self-assembling-peptide-amphiphiles
#18
Akihiro J Matsuoka, Zafar A Sayed, Nicholas Stephanopoulos, Eric J Berns, Anil R Wadhwani, Zachery D Morrissey, Duncan M Chadly, Shun Kobayashi, Alexandra N Edelbrock, Tomoji Mashimo, Charles A Miller, Tammy L McGuire, Samuel I Stupp, John A Kessler
The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears...
2017: PloS One
https://www.readbyqxmd.com/read/29282583/high-quality-human-preimplantation-embryos-actively-influence-endometrial-stromal-cell-migration
#19
R P Berkhout, C B Lambalk, J Huirne, V Mijatovic, S Repping, G Hamer, S Mastenbroek
PURPOSE: The purpose of this paper is to study whether human preimplantation embryos regulate endometrial stromal cell (hESC) migration. METHODS: Primary hESCs were isolated from fertile patients undergoing hysterectomy for benign conditions (uterine scar niche n = 3, dysmenorrhea n = 2; no hormonal treatment). Migration and proliferation assays were performed by culturing decidualized or non-decidualized hESCs in the presence of embryo conditioned medium (ECM) from high-quality embryos (fragmentation ≤ 20%) or from low-quality embryos (fragmentation > 20%) or in non-conditioned medium from the same dishes (control)...
December 28, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29279011/recombinant-extracellular-matrix-protein-fragments-support-human-embryonic-stem-cell-chondrogenesis
#20
Aixin Cheng, Stuart Alan Cain, Pinyuan Tian, Andrew K Baldwin, Paweena Uppanan, Cay M Kielty, Susan J Kimber
We previously developed a 14-day culture protocol under potentially GMP, chemically defined conditions, to generate chondro-progenitors from human embryonic stem cells (hESCs). In vivo work has confirmed the cartilage repair capacity of these cells in a nude rat osteochondral defect model. Aiming to enhance hESC-chondrogenesis we screened a range of extracellular matrix (ECM) molecules for their ability to support differentiation of hESCs towards chondrocytes. We identified two novel ECM protein fragments that supported hESC-chondrogenesis: Fibronectin III (fibronectin 7-14 protein fragments including the RGD domain, syndecan binding domain and heparin binding domain); fibrillin-1 (FBN1) fragment PF8 (encoded by exons 30-38, residues 1238-1605, which contains the RGD motif but not heparin binding site)...
December 27, 2017: Tissue Engineering. Part A
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