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https://www.readbyqxmd.com/read/27906170/generating-high-purity-cardiac-and-endothelial-derivatives-from-patterned-mesoderm-using-human-pluripotent-stem-cells
#1
Nathan J Palpant, Lil Pabon, Clayton E Friedman, Meredith Roberts, Brandon Hadland, Rebecca J Zaunbrecher, Irwin Bernstein, Ying Zheng, Charles E Murry
Human pluripotent stem cells (hPSCs) provide a valuable model for the study of human development and a means to generate a scalable source of cells for therapeutic applications. This protocol specifies cell fate efficiently into cardiac and endothelial lineages from hPSCs. The protocol takes 2 weeks to complete and requires experience in hPSC culture and differentiation techniques. Building on lessons taken from early development, this monolayer-directed differentiation protocol uses different concentrations of activin A and bone morphogenetic protein 4 (BMP4) to polarize cells into mesodermal subtypes that reflect mid-primitive-streak cardiogenic mesoderm and posterior-primitive-streak hemogenic mesoderm...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27906098/direct-reprogramming-of-urine-derived-cells-with-inducible-myod-for-modeling-human-muscle-disease
#2
Ellis Y Kim, Patrick Page, Lisa M Dellefave-Castillo, Elizabeth M McNally, Eugene J Wyatt
BACKGROUND: Cellular models of muscle disease are taking on increasing importance with the large number of genes and mutations implicated in causing myopathies and the concomitant need to test personalized therapies. Developing cell models relies on having an easily obtained source of cells, and if the cells are not derived from muscle itself, a robust reprogramming process is needed. Fibroblasts are a human cell source that works well for the generation of induced pluripotent stem cells, which can then be differentiated into cardiomyocyte lineages, and with less efficiency, skeletal muscle-like lineages...
September 15, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906085/tissue-engineered-cardiac-patch-seeded-with-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-promoted-the-regeneration-of-host-cardiomyocytes-in-a-rat-model
#3
Tadahisa Sugiura, Narutoshi Hibino, Christopher K Breuer, Toshiharu Shinoka
BACKGROUND: Thousands of babies are born with congenital heart defects that require surgical repair involving a prosthetic implant. Lack of growth in prosthetic grafts is especially detrimental in pediatric surgery. Cell seeded biodegradable tissue engineered grafts are a novel solution to this problem. The purpose of the present study is to evaluate the feasibility of seeding human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) onto a biodegradable cardiac patch. METHODS: The hiPS-CMs were cultured on a biodegradable patch composed of a polyglycolic acid (PGA) and a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) for 1 week...
December 1, 2016: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/27906056/umbilical-cord-blood-derived-non-hematopoietic-stem-cells-retrieved-and-expanded-on-bone-marrow-derived-extracellular-matrix-display-pluripotent-characteristics
#4
Junjie Wu, Yun Sun, Travis J Block, Milos Marinkovic, Zhi-Liang Zhang, Richard Chen, Yixia Yin, Juquan Song, David D Dean, Zhongding Lu, Xiao-Dong Chen
BACKGROUND: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces. METHODS AND RESULTS: In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27905670/induced-pluripotent-stem-cells-as-a-new-getaway-for-bone-tissue-engineering-a-systematic-review
#5
REVIEW
Farshid Bastami, Pantea Nazeman, Hamidreza Moslemi, Maryam Rezai Rad, Kazem Sharifi, Arash Khojasteh
OBJECTIVES: Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising alternative source for bone regeneration. This study aimed to systematically review the available literature on osteogenic potential of iPSCs and to discuss methods applied to enhance their osteogenic potential...
December 1, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27905261/beneath-the-sword-of-damocles-regenerative-medicine-and-the-shadow-of-immunogenicity
#6
Paul J Fairchild, Christopher Horton, Priyoshi Lahiri, Kumaran Shanmugarajah, Timothy J Davies
Few topics in regenerative medicine have inspired such impassioned debate as the immunogenicity of cell types and tissues differentiated from pluripotent stem cells. While early predictions suggested that tissues derived from allogeneic sources may evade immune surveillance altogether, the pendulum has since swung to the opposite extreme, with reports that the ectopic expression of a few developmental antigens may prompt rejection, even of tissues differentiated from autologous cell lines. Here we review the evidence on which these contradictory claims are based in order to reach an objective assessment of the likely magnitude of the immunological challenges ahead...
December 1, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#7
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904680/enhancement-of-early-cardiac-differentiation-of-dedifferentiated-fat-cells-by-dimethyloxalylglycine-via-notch-signaling-pathway
#8
Fuhai Li, Zongzhuang Li, Zhi Jiang, Ye Tian, Zhi Wang, Wei Yi, Chenyun Zhang
Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904501/human-amniotic-epithelial-cells-combined-with-silk-fibroin-scaffold-in-the-repair-of-spinal-cord-injury
#9
Ting-Gang Wang, Jie Xu, Ai-Hua Zhu, Hua Lu, Zong-Ning Miao, Peng Zhao, Guo-Zhen Hui, Wei-Jiang Wu
Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithelial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903222/sustained-elabela-gene-therapy-in-high-salt-induced-hypertensive-rats
#10
Claire A Schreiber, Sara J Holditch, Alex Generous, Yasuhiro Ikeda
BACKGROUND: Elabela (ELA) is a recently identified apelin receptor agonist essential for cardiac development, but its biology and therapeutic potential are unclear. In humans ELA transcripts are detected in embryonic stem cells, induced pluripotent stem cells, kidney, heart and blood vessels. ELA through the apelin receptor promotes angiogenesis in vitro, relaxes murine aortic blood vessels and attenuates high blood pressure in vivo. The apelin receptor when bound to its original ligand, apelin, exerts peripheral vasodilatory and positive inotropic effects, conferring cardioprotection in vivo...
November 21, 2016: Current Gene Therapy
https://www.readbyqxmd.com/read/27903111/electric-stimulation-enhances-cardiac-differentiation-of-human-induced-pluripotent-stem-cells-for-myocardial-infarction-therapy
#11
Ruilian Ma, Jialiang Liang, Wei Huang, Linlin Guo, WenFeng Cai, Lei Wang, Christian Paul, Huang-Tian Yang, Ha Won Kim, Yigang Wang
AIM: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI). RESULTS: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation. Spontaneously beating hiPSCs were observed as early at 2 days when treated with EleS as compared to control treatment...
November 30, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27900874/human-pluripotent-stem-cells-in-modeling-human-disorders-the-case-of-fragile-x-syndrome
#12
Dan Vershkov, Nissim Benvenisty
Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS...
November 30, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27900567/clinical-potential-of-human-induced-pluripotent-stem-cells-perspectives-of-induced-pluripotent-stem-cells
#13
REVIEW
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
November 29, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27899656/idp-ase-haplotyping-and-quantifying-allele-specific-expression-at-the-gene-and-gene-isoform-level-by-hybrid-sequencing
#14
Benjamin Deonovic, Yunhao Wang, Jason Weirather, Xiu-Jie Wang, Kin Fai Au
Allele-specific expression (ASE) is a fundamental problem in studying gene regulation and diploid transcriptome profiles, with two key challenges: (i) haplotyping and (ii) estimation of ASE at the gene isoform level. Existing ASE analysis methods are limited by a dependence on haplotyping from laborious experiments or extra genome/family trio data. In addition, there is a lack of methods for gene isoform level ASE analysis. We developed a tool, IDP-ASE, for full ASE analysis. By innovative integration of Third Generation Sequencing (TGS) long reads with Second Generation Sequencing (SGS) short reads, the accuracy of haplotyping and ASE quantification at the gene and gene isoform level was greatly improved as demonstrated by the gold standard data GM12878 data and semi-simulation data...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899508/optimized-inducible-shrna-and-crispr-cas9-platforms-for-in-vitro-studies-of-human-development-using-hpscs
#15
Alessandro Bertero, Matthias Pawlowski, Daniel Ortmann, Kirsten Snijders, Loukia Yiangou, Miguel Cardoso de Brito, Stephanie Brown, William G Bernard, James D Cooper, Elisa Giacomelli, Laure Gambardella, Nicholas R F Hannan, Dharini Iyer, Fotios Sampaziotis, Felipe Serrano, Mariëlle C F Zonneveld, Sanjay Sinha, Mark Kotter, Ludovic Vallier
Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms. These are based on genetic engineering of human genomic safe harbors combined with an improved tetracycline-inducible system and CRISPR/Cas9 technology...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27899507/cycling-through-developmental-decisions-how-cell-cycle-dynamics-control-pluripotency-differentiation-and-reprogramming
#16
REVIEW
Abdenour Soufi, Stephen Dalton
A strong connection exists between the cell cycle and mechanisms required for executing cell fate decisions in a wide-range of developmental contexts. Terminal differentiation is often associated with cell cycle exit, whereas cell fate switches are frequently linked to cell cycle transitions in dividing cells. These phenomena have been investigated in the context of reprogramming, differentiation and trans-differentiation but the underpinning molecular mechanisms remain unclear. Most progress to address the connection between cell fate and the cell cycle has been made in pluripotent stem cells, in which the transition through mitosis and G1 phase is crucial for establishing a window of opportunity for pluripotency exit and the initiation of differentiation...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#17
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27898091/restoring-ureagenesis-in-hepatocytes-by-crispr-cas9-mediated-genomic-addition-to-arginase-deficient-induced-pluripotent-stem-cells
#18
Patrick C Lee, Brian Truong, Agustin Vega-Crespo, W Blake Gilmore, Kip Hermann, Stephanie Ak Angarita, Jonathan K Tang, Katherine M Chang, Austin E Wininger, Alex K Lam, Benjamen E Schoenberg, Stephen D Cederbaum, April D Pyle, James A Byrne, Gerald S Lipshutz
Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27898090/lips-a3s-a-human-genomic-site-for-robust-expression-of-inserted-transgenes
#19
Andriana G Kotini, Michel Sadelain, Eirini P Papapetrou
Transgenesis of human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. While in recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. In order to find human genomic sites capable of supporting long-term and high-level transgene expression in hPSCs, we performed a lentiviral screen in human induced pluripotent stem cells (iPSCs)...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27897204/human-mitochondrial-transcriptional-factor-a-breaks-the-mitochondria-mediated-vicious-cycle-in-alzheimer-s-disease
#20
Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu
In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA)...
November 29, 2016: Scientific Reports
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