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https://www.readbyqxmd.com/read/28811655/a-tissue-engineered-blood-vessel-model-of-hutchinson-gilford-progeria-syndrome-using-human-ipsc-derived-smooth-muscle-cells
#1
Leigh Atchison, Haoyue Zhang, Kan Cao, George A Truskey
Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794109/comparative-study-on-glucose-transporters-expression-and-activity-between-stem-cell-derived-brain-microvascular-endothelial-cells-and-hcmec-d3-cells
#2
Abraham J Al-Alahmad
Glucose constitutes the major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 is associated with the GLUT1 deficiency syndrome (GLUT1DS), yet none of the current in vitro models of the human BBB maybe suited for modelling such disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across the human BBB using brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs)...
August 9, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28774343/effect-of-shear-stress-on-ipsc-derived-human-brain-microvascular-endothelial-cells-dhbmecs
#3
Jackson G DeStefano, Zinnia S Xu, Ashley J Williams, Nahom Yimam, Peter C Searson
BACKGROUND: The endothelial cells that form the lumen of capillaries and microvessels are an important component of the blood-brain barrier. Cell phenotype is regulated by transducing a range of biomechanical and biochemical signals in the local microenvironment. Here we report on the role of shear stress in modulating the morphology, motility, proliferation, apoptosis, and protein and gene expression, of confluent monolayers of human brain microvascular endothelial cells derived from induced pluripotent stem cells...
August 4, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28771372/high-content-assay-multiplexing-for-vascular-toxicity-screening-in-induced-pluripotent-stem-cell-derived-endothelial-cells-and-human-umbilical-vein-endothelial-cells
#4
Yasuhiro Iwata, William D Klaren, Connie S Lebakken, Fabian A Grimm, Ivan Rusyn
Endothelial cells (ECs) play a major role in blood vessel formation and function. While there is longstanding evidence for the potential of chemical exposures to adversely affect EC function and vascular development, the hazard potential of chemicals with respect to vascular effects is not routinely evaluated in safety assessments. Induced pluripotent stem cell (iPSC)-derived ECs promise to provide a physiologically relevant, organotypic culture model that is amenable for high-throughput (HT) EC toxicant screening and may represent a viable alternative to traditional in vitro models, including human umbilical vein endothelial cells (HUVECs)...
August 3, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28765558/cardiac-spheroids-as-promising-in-vitro-models-to-study-the-human-heart-microenvironment
#5
Liudmila Polonchuk, Mamta Chabria, Laura Badi, Jean-Christophe Hoflack, Gemma Figtree, Michael J Davies, Carmine Gentile
Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present in vivo. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757162/an-in%C3%A2-vitro-human-liver-model-by-ipsc-derived-parenchymal-and-non-parenchymal-cells
#6
Yuta Koui, Taketomo Kido, Toshimasa Ito, Hiroki Oyama, Shin-Wei Chen, Yuki Katou, Katsuhiko Shirahige, Atsushi Miyajima
During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor β and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28743464/stem-cell-therapy-for-abrogating-stroke-induced-neuroinflammation-and-relevant-secondary-cell-death-mechanisms
#7
REVIEW
Connor Stonesifer, Sydney Corey, Shaila Ghanekar, Zachary Diamandis, Sandra A Acosta, Cesar V Borlongan
Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation...
July 22, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28628273/exposure-of-induced-pluripotent-stem-cell-derived-vascular-endothelial-and-smooth-muscle-cells-in-coculture-to-hemodynamics-induces-primary-vascular-cell-like-phenotypes
#8
Maria S Collado, Banumathi K Cole, Robert A Figler, Mark Lawson, David Manka, Michael B Simmers, Steve Hoang, Felipe Serrano, Brett R Blackman, Sanjay Sinha, Brian R Wamhoff
Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. However, because iECs and iSMCs are not derived from an intact blood vessel, they represent an immature phenotype. Hemodynamics and heterotypic cell:cell communication play important roles in vascular cell phenotypic modulation. Here we tested the hypothesis that hemodynamic exposure of iECs in coculture with iSMCs induces an in vivo-like phenotype. iECs and iSMCs were cocultured under vascular region-specific blood flow hemodynamics, and compared to hemodynamic cocultures of blood vessel-derived endothelial (pEC) and smooth muscle (pSMC) cells...
August 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28602946/whole-genome-analysis-reveals-unexpected-dynamics-of-mutant-subclone-development-in-a-patient-with-jak2-v617f-positive-chronic-myeloid-leukemia
#9
Ivan Sloma, Maria Teresa Mitjavila-Garcia, Olivier Feraud, Frank Griscelli, Noufissa Oudrhiri, Sanaa El Marsafy, Emilie Gobbo, Dominique Divers, Alexis Proust, David M Smadja, Christophe Desterke, Annaick Carles, Yusanna Ma, Martin Hirst, Marco A Marra, Connie J Eaves, Annelise Bennaceur-Griscelli, Ali G Turhan
We report here the first use of whole-genome sequencing (WGS) to examine the initial clonal dynamics in an unusual patient with chronic myeloid leukemia (CML), who presented in chronic phase (CP) with doubly marked BCR-ABL1(+)/JAK2(V617F)-mutant cells and, over a 9-year period, progressed into an accelerated phase (AP) and then terminal blast phase (BP). WGS revealed that the diagnostic cells also contained mutations in ASXL1, SEC23B, MAD1L1, and RREB1 as well as 12,000 additional uncommon DNA variants. WGS of endothelial cells generated from circulating precursors revealed many of these were shared with the CML clone...
June 8, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28524367/transplantation-of-human-villous-trophoblasts-preserves-cardiac-function-in-mice-with-acute-myocardial-infarction
#10
Zegen Wang, Ningzheng Dong, Yayan Niu, Zhiwei Zhang, Ce Zhang, Meng Liu, Tiantian Zhou, Qingyu Wu, Ke Cheng
Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#11
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28505174/extracellular-matrix-nitration-alters-growth-factor-release-and-activates-bioactive-complement-in-human-retinal-pigment-epithelial-cells
#12
Mark A Fields, Hannah E Bowrey, Jie Gong, Ernesto F Moreira, Hui Cai, Lucian V Del Priore
PURPOSE: We have shown previously that non-enzymatic nitration (NEN) of the extracellular matrix (ECM), which serves as a model of Bruch's membrane (BM) aging, has a profound effect on the behavior of the overlying retinal pigment epithelial (RPE) cells, including altered phagocytic ability, reduced cell adhesion, and inhibition of proliferation. We know that transplanted RPE monolayers will encounter a hostile sub-RPE environment, including age-related alterations in BM that may compromise cell function and survival...
2017: PloS One
https://www.readbyqxmd.com/read/28474838/connective-tissue-growth-factor-promotes-efficient-generation-of-human-induced-pluripotent-stem-cell-derived-choroidal-endothelium
#13
Allison E Songstad, Kristan S Worthington, Kathleen R Chirco, Joseph C Giacalone, S Scott Whitmore, Kristin R Anfinson, Dalyz Ochoa, Cathryn M Cranston, Megan J Riker, Maurine Neiman, Edwin M Stone, Robert F Mullins, Budd A Tucker
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, the majority of stem cell research to date has focused on production of retinal pigment epithelial (RPE) and photoreceptor cells for the purpose of evaluating disease pathophysiology and cell replacement, there is strong evidence that the choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first to be lost in this disease. As such, to accurately evaluate disease pathophysiology and develop an effective treatment, production of patient-specific, stem cell-derived CECs will be required...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28407791/accelerated-differentiation-of-human-induced-pluripotent-stem-cells-to-blood-brain-barrier-endothelial-cells
#14
Emma K Hollmann, Amanda K Bailey, Archit V Potharazu, M Diana Neely, Aaron B Bowman, Ethan S Lippmann
BACKGROUND: Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB), for research purposes. Unfortunately, the time, expense, and expertise required to differentiate iPSCs to purified BMECs precludes their widespread use. Here, we report the use of a defined medium that accelerates the differentiation of iPSCs to BMECs while achieving comparable performance to BMECs produced by established methods...
April 13, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28397247/isogenic-blood-brain-barrier-models-based-on-patient-derived-stem-cells-display-inter-individual-differences-in-cell-maturation-and-functionality
#15
Ronak Patel, Shyanne Page, Abraham Jacob Al-Ahmad
The blood-brain barrier (BBB) constitutes an important component of the neurovascular unit formed by specialized brain microvascular endothelial cells (BMECs) surrounded by astrocytes, pericytes, and neurons. Recently, isogenic in vitro models of the BBB based on human pluripotent stem cells have been documented, yet the impact of inter-individual variability on the yield and phenotype of such models remains to be documented. In this study, we investigated the impact of inter-individual variability on the yield and phenotype of isogenic models of the BBB, using patient-derived induced pluripotent stem cells (iPSCs)...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28396709/human-ipsc-derived-myocardium-on-chip-with-capillary-like-flow-for-personalized-medicine
#16
Bradley W Ellis, Aylin Acun, U Isik Can, Pinar Zorlutuna
The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current in vitro models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells...
March 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28361320/liver-regeneration-using-cultured-liver-bud
#17
Keisuke Sekine, Takanori Takebe, Hideki Taniguchi
Here, we describe a protocol to develop a three-dimensional (3D) liver bud-like tissue from human iPSCs in vitro. This method mainly consists of two parts: (1) hepatic endoderm (HE) differentiation from human iPSCs in 2D culture and (2) co-culturing iPSC-HE with endothelial and mesenchymal cells. First, iPSCs were differentiated into definitive endoderm (DE) cells, and the DE cells were differentiated into HE cells, which were then co-cultured with endothelial cells and mesenchymal cells on Matrigel-coated plastic plates or micropattern plates...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#18
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
May 2017: Gene Therapy
https://www.readbyqxmd.com/read/28286868/a-basis-for-comparison-sensitive-authentication-of-stem-cell-derived-rpe-using-physiological-responses-of-intact-rpe-monolayers
#19
Kiyoharu J Miyagishima, Qin Wan, Sheldon S Miller, Kapil Bharti
The retinal pigment epithelium (RPE) is a monolayer of highly specialized cells that help maintain the chemical composition of its surrounding subretinal and choroidal extracellular spaces. Retinal cells (photoreceptors in particular), RPE, and choroidal endothelial cells together help ensure a homeostatically stable metabolic environment with exquisitely sensitive functional responses to light. Aging and disease of the RPE impairs its supportive functions contributing to the progressive loss of photoreceptors and vision...
2017: Stem Cell and Translational Investigation
https://www.readbyqxmd.com/read/28281438/engineered-microvasculature-in-pdms-networks-using-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells
#20
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 PDMS-based platform for the generation of intact, perfusioncompetent microvessel networks <i>in vitro</i>. COMSOL Multiphysics, a finite element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human iPSCs were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 days under completely chemically defined conditions, using the small molecule GSK3β inhibitor CHIR99021 and thoroughly characterized for functionality and arteriallike marker expression...
March 9, 2017: Cell Transplantation
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