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https://www.readbyqxmd.com/read/28934733/exosomes-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-liver-against-hepatic-ischemia-reperfusion-injury-via-activating-sphingosine-kinase-and-sphingosine-1-phosphate-signaling-pathway
#1
Yingdong Du, Dawei Li, Conghui Han, Haoyu Wu, Longmei Xu, Ming Zhang, Jianjun Zhang, Xiaosong Chen
BACKGROUND/AIMS: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury, as well as the underlying mechanisms. METHODS: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934500/a-synthetic-dna-binding-inhibitor-of-sox2-guides-human-induced-pluripotent-stem-cells-to-differentiate-into-mesoderm
#2
Junichi Taniguchi, Ganesh N Pandian, Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Kyeong Kyu Kim, Hiroshi Sugiyama
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#3
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28925369/generation-of-a-gene-corrected-isogenic-control-ipsc-line-from-cystic-fibrosis-patient-specific-ipscs-homozygous-for-p-phe508del-mutation-mediated-by-talens-and-ssodn
#4
Sylvia Merkert, Christien Bednarski, Gudrun Göhring, Toni Cathomen, Ulrich Martin
Cystic fibrosis (CF) is a monogenetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which affects multiple organs. Human induced pluripotent stem cells (iPSCs) derived from CF patients and the generation of isogeneic gene-corrected control cell lines enable disease modelling, drug discovery or toxicological studies and therefore the development of CF patient-specific therapies. We have previously generated a hiPSC line from a CF patient homozygous for the p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925368/a-marfan-syndrome-human-induced-pluripotent-stem-cell-line-with-a-heterozygous-fbn1-c-4082g-a-mutation-ismmsi002-b-for-disease-modeling
#5
Sandra Klein, Jill L Dvornik, Akshitha R Yarrabothula, Christoph Schaniel
Fibroblasts of a 28-year-old female with Marfan syndrome (MFS) due to a heterozygous FBN1 c.4082G>A mutation were reprogrammed using the Sendai virus delivery method. The established human induced pluripotent stem cell (hiPSC) line named ISMMSi002-B expresses pluripotency markers, has a normal karyotype, carries the specific FBN1 mutation and is able to differentiate into three germ layers in vitro. ISMMSi002-B has utility in studying MFS pathogenesis, including skeletal abnormalities, cardiomyopathy, and vascular smooth muscle cell dysfunction associated with aortic aneurysm...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925359/generation-of-an-oct4-reporter-human-induced-pluripotent-stem-cell-line-using-crispr-spcas9
#6
Diego Balboa, Jere Weltner, Yuval Novik, Solja Eurola, Kirmo Wartiovaara, Timo Otonkoski
OCT4 is a crucial transcription factor in the pluripotent stem cell gene regulatory network and an essential factor for pluripotent reprogramming. We engineered the previously reported HEL24.3 hiPSC to generate an OCT4 reporter cell line by knocking-in a T2A nuclear EmGFP reporter cassette before the OCT4 gene STOP codon sequence. To enhance targeted insertion, homologous recombination was stimulated using targeted cutting at the OCT4 STOP codon with CRISPR/SpCas9. This HEL24.3-OCT4-nEmGFP cell line faithfully reports endogenous OCT4 expression, serving as a useful tool to examine temporal changes in OCT4 expression in live cells during hiPSC culture, differentiation and somatic cell reprogramming...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924979/quantification-of-etoposide-hypersensitivity-a-sensitive-functional-method-for-assessing-pluripotent-stem-cell-quality
#7
Frank J Secreto, Xing Li, Alyson J Smith, Elizabeth S Bruinsma, Ester Perales-Clemente, Saji Oommen, Gresin Hawse, Sybil C L Hrstka, Bonnie K Arendt, Emma B Brandt, Dennis A Wigle, Timothy J Nelson
Human induced pluripotent stem cells (hiPSC) hold great promise in diagnostic and therapeutic applications. However, translation of hiPSC technology depends upon a means of assessing hiPSC quality that is quantitative, high-throughput, and can decipher malignant teratocarcinoma clones from normal cell lines. These attributes are lacking in current approaches such as detection of cell surface makers, RNA profiling, and/or teratoma formation assays. The latter remains the gold standard for assessing clone quality in hiPSCs, but is expensive, time-consuming, and incompatible with high-throughput platforms...
September 19, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28924210/kinase-inhibitor-screening-using-artificial-neural-networks-and-engineered-cardiac-biowires
#8
Genevieve Conant, Samad Ahadian, Yimu Zhao, Milica Radisic
Kinase inhibitors are often used as cancer targeting agents for their ability to prevent the activation of cell growth and proliferation signals. Cardiotoxic effects have been identified for some marketed kinase inhibitors that were not detected during clinical trials. We hypothesize that more predictive cardiac functional assessments of kinase inhibitors on human myocardium can be established by combining a high-throughput two-dimensional (2D) screening assay and a high-content three-dimensional (3D) engineered cardiac tissue (Biowire(TM)) based assay, and using human induced pluripotent stem cell-derived CMs (hiPSC-CMs)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921822/construction-of-human-induced-pluripotent-stem-cell-derived-oriented-bone-matrix-microstructure-by-using-in-vitro-engineered-anisotropic-culture-model
#9
Ryosuke Ozasa, Aira Matsugaki, Yoshihiro Isobe, Taro Saku, Hui-Suk Yun, Takayoshi Nakano
Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold...
September 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#10
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28901188/engineered-microvasculature-in-pdms-networks-using-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells
#11
Amogh Sivarapatna, Mahboobe Ghaedi, Yang Xiao, Edward Han, Binod Aryal, Jing Zhou, Carlos Fernandez-Hernando, Yibing Qyang, Karen K Hirschi, Laura E Niklason
In this study, we used a polydimethylsiloxane (PDMS)-based platform for the generation of intact, perfusion-competent microvascular networks in vitro. COMSOL Multiphysics, a finite-element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human induced pluripotent stem cells (hiPSCs) were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 d under completely chemically defined conditions, using the small molecule glycogen synthase kinase 3β inhibitor CHIR99021 and were thoroughly characterized for functionality and arterial-like marker expression...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28883014/human-pluripotent-stem-cell-models-of-cardiac-disease-from-mechanisms-to-therapies
#12
REVIEW
Karina O Brandão, Viola A Tabel, Douwe E Atsma, Christine L Mummery, Richard P Davis
It is now a decade since human induced pluripotent stem cells (hiPSCs) were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies...
September 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28880276/lncrna-znf503-as1-promotes-rpe-differentiation-by-downregulating-znf503-expression
#13
Xue Chen, Chao Jiang, Bing Qin, Guohua Liu, Jiangdong Ji, Xiantao Sun, Min Xu, Sijia Ding, Meidong Zhu, Guofu Huang, Biao Yan, Chen Zhao
Long noncoding RNAs (lncRNAs) have important roles in various biological processes. Our previous work has revealed that dedifferentiation of retinal pigment epithelium (RPE) cells contributes to the pathology of age-related macular degeneration (AMD). Herein, we show roles of lncRNAs in RPE differentiation. We used microarray to identify lncRNA expression profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived RPE cells. A total of 217 differentially expressed lncRNAs along with the differentiation were initially identified, among which 13 lncRNAs showed a consistent fold change of over 2...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28880155/identification-of-ion-currents-components-generating-field-potential-recorded-in-mea-from-hipsc-cm
#14
Fabien Raphel, Muriel Boulakia, Nejib Zemzemi, Yves Coudiere, Jean-Michel Guillon, Philippe Zitoun, Jean-Frederic Gerbeau
Multi Electrodes Arrays (MEAs) combined with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) can enable high- or medium-throughput drug screening in safety pharmacology. This technology has recently attracted a lot of attention, in particular from an international initiative named CiPA. But it is currently limited by the difficulty to analyze the measured signals. We propose a strategy to analyze the signals acquired by the MEA and to automatically deduce the channels affected by the drug...
September 4, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28878022/drusen-in-patient-derived-hipsc-rpe-models-of-macular-dystrophies
#15
Chad A Galloway, Sonal Dalvi, Sandy S C Hung, Leslie A MacDonald, Lisa R Latchney, Raymond C B Wong, Robyn H Guymer, David A Mackey, David S Williams, Mina M Chung, David M Gamm, Alice Pébay, Alex W Hewitt, Ruchira Singh
Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases...
September 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28876908/three-dimensional-electroconductive-hyaluronic-acid-hydrogels-incorporated-with-carbon-nanotubes-and-polypyrrole-by-catechol-mediated-dispersion-enhance-neurogenesis-of-human-neural-stem-cells
#16
Jisoo Shin, Eun Jung Choi, Jung Ho Cho, Ann-Na Cho, Yoonhee Jin, Kisuk Yang, Changsik Song, Seung-Woo Cho
Electrically conductive hyaluronic acid (HA) hydrogels incorporated with single-walled carbon nanotubes (CNTs) and/or polypyrrole (PPy) were developed to promote differentiation of human neural stem/progenitor cells (hNSPCs). The CNT and PPy nanocomposites, which do not easily disperse in aqueous phases, dispersed well and were efficiently incorporated into catechol-functionalized HA (HA-CA) hydrogels by the oxidative catechol chemistry used for hydrogel crosslinking. The prepared electroconductive HA hydrogels provided dynamic, electrically conductive three-dimensional (3D) extracellular matrix environments that were biocompatible with hNSPCs...
September 6, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28875579/a-cardiac-patch-from-aligned-microvessel-and-cardiomyocyte-patches
#17
Jeremy A Schaefer, Pilar A Guzman, Sonja B Riemenschneider, Timothy J Kamp, Robert T Tranquillo
Cardiac tissue engineering aims to produce replacement tissue patches in the lab to replace or treat infarcted myocardium. However, current patches lack pre-formed microvascularization and are therefore limited in thickness and force production. In the present study, we sought to assess whether a bi-layer patch composed of a layer made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a microvessel layer composed of self-assembled human blood outgrowth endothelial cells (BOECs) and pericytes (PCs) was capable of engrafting on the epicardial surface of a nude rat infarct model and becoming perfused by the host four weeks after acute implantation...
September 5, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28867785/patch-clamp-recording-from-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-improving-action-potential-characteristics-through-dynamic-clamp
#18
Arie O Verkerk, Christiaan C Veerman, Jan G Zegers, Isabella Mengarelli, Connie R Bezzina, Ronald Wilders
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in "ventricular-like" and "atrial-like" hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette)...
August 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28859296/human-induced-pluripotent-stem-cell-derived-vascular-smooth-muscle-cells-differentiation-and-therapeutic-potential
#19
Sohrab Ayoubi, Søren P Sheikh, Tilde V Eskildsen
Cardiovascular diseases remain the leading cause of death worldwide and current treatment strategies have limited effect of disease progression. It would be desirable to have better models to study developmental and pathological processes and model vascular diseases in laboratory settings. To this end, human induced pluripotent stem cells (hiPSCs) have generated great enthusiasm, and have been a driving force for development of novel strategies in drug discovery and regenerative cell-therapy for the last decade...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28855280/in-vitro-and-in-vivo-imaging-and-tracking-of-intestinal-organoids-from-human-induced-pluripotent-stem-cells
#20
Kwang Bo Jung, Hana Lee, Ye Seul Son, Ji Hye Lee, Hyun-Soo Cho, Mi-Ok Lee, Jung-Hwa Oh, Jaemin Lee, Seokho Kim, Cho-Rok Jung, Janghwan Kim, Mi-Young Son
Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human-induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters (KLF5(mCherry) and ISX(eGFP)). Then hIOs were efficiently induced from those transgenic hiPSC lines in which monomeric Cherry- or enhanced green fluorescent protein-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time...
August 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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