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Ipsc endothelial

Deguang Yang, Jinhong Wang, Meng Xiao, Tao Zhou, Xu Shi
Stem-cell-based therapy for cardiovascular disease, especially ischemic heart disease (IHD), is a promising approach to facilitating neovascularization through the migration of stem cells to the ischemic site and their subsequent differentiation into endothelial cells (ECs). Hypoxia is a chief feature of IHD and the stem cell niche. However, whether hypoxia promotes stem cell differentiation into ECs or causes them to retain their stemness is controversial. Here, the differentiation of pluripotent stem cells (iPSCs) into endothelial cells (ECs) was induced under hypoxia...
October 12, 2016: Scientific Reports
Marta Prieto-Vila, Ting Yan, Anna Sanchez Calle, Neha Nair, Laura Hurley, Tomonari Kasai, Hiroki Kakuta, Junko Masuda, Hiroshi Murakami, Akifumi Mizutani, Masaharu Seno
To grow beyond a size of approximately 1-2 mm(3), tumor cells activate many processes to develop blood vasculature. Growing evidences indicate that the formation of the tumor vascular network is very complex, and is not restricted to angiogenesis. Cancer cell-derived tumor vasculatures have been recently described. Among them, endothelial differentiation of tumor cells have been directly related to cancer stem cells, which are cells within a tumor that possess the capacity to self-renew, and to exhibit multipotential heterogeneous lineages of cancer cells...
2016: American Journal of Cancer Research
Shuji Hamauchi, Hideo Shichinohe, Haruto Uchino, Shigeru Yamaguchi, Naoki Nakayama, Ken Kazumata, Toshiya Osanai, Takeo Abumiya, Kiyohiro Houkin, Takumi Era
BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a slow, progressive steno-occlusive disease, arising in the terminal portions of the cerebral internal carotid artery. However, the functions and characteristics of the endothelial cells (ECs) in MMD are unknown. We analyzed these features using induced pluripotent stem cell (iPSC)-derived ECs. METHODS: iPSC lines were established from the peripheral blood of three patients with MMD carrying the variant RNF213 R4810K, and three healthy persons used as controls...
2016: PloS One
Neli Kachamakova-Trojanowska, Witold Nowak, Krzysztof Szade, Jacek Stepniewski, Karolina Bukowska-Strakova, Monika Zukowska, Hevidar Taha, Antonina Chmura-Skirlinska, Michael Beilharz, Jozef Dulak, Alicja Jozkowicz
Induced pluripotent stem cells (iPSCs) have shown great potential in regenerative medicine and research applications like disease modeling or drug discovery. Endothelium is indispensable for vascular homeostasis, whereas endothelial dysfunction could lead to different diseases. Therefore, generating autologous cells, able to restore the endothelial lining, can be crucial for slowing or reversing certain pathological processes. In the current study we show efficient differentiation of murine iPSCs into endothelial cells (ECs) with stable CD34+/Tie-2+/Sca-1+/CD45- phenotype and proven functionality...
August 25, 2016: Vascular Pharmacology
Emilie Barruet, Blanca M Morales, Wint Lwin, Mark P White, Christina V Theodoris, Hannah Kim, Ashley Urrutia, Sarah Anne Wong, Deepak Srivastava, Edward C Hsiao
BACKGROUND: The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if and how this occurs in human endothelial cells remains unclear. METHODS: We used a new directed differentiation protocol to create human induced pluripotent stem cell (hiPSC)-derived endothelial cells (iECs) from patients with fibrodysplasia ossificans progressiva (FOP), a congenital disease of heterotopic ossification caused by an activating R206H mutation in the Activin A type I receptor (ACVR1)...
2016: Stem Cell Research & Therapy
Daniel Alejandro Lerman, Nasri Alotti, Kiddy Levente Ume, Bruno Péault
Ischaemic heart disease is the predominant contributor to cardiovascular morbidity and mortality; one million myocardial Infarctions occur per year in the USA, while more than five million patients suffer from chronic heart failure. Recently, heart failure has been singled out as an epidemic and is a staggering clinical and public health problem associated with significant mortality, morbidity and healthcare expenditures, particularly among those aged ≥65 years. Death rates have improved dramatically over the last four decades, but new approaches are nevertheless urgently needed for those patients who go on to develop ventricular dysfunction and chronic heart failure...
2016: European Cardiology
Luqia Hou, John Coller, Vanita Natu, Trevor J Hastie, Ngan F Huang
UNLABELLED: Recent developments in cell therapy using human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) hold great promise for treating ischemic cardiovascular tissues. However, poor post-transplantation viability largely limits the potential of stem cell therapy. Although the extracellular matrix (ECM) has become increasingly recognized as an important cell survival factor, conventional approaches primarily rely on single ECMs for in vivo co-delivery with cells, even though the endothelial basement membrane is comprised of a milieu of different ECMs...
October 15, 2016: Acta Biomaterialia
Paul A Clark, Abraham J Al-Ahmad, Tongcheng Qian, Ray R Zhang, Hannah K Wilson, Jamey P Weichert, Sean P Palecek, John S Kuo, Eric V Shusta
Cancer-targeting alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure-activity studies. While they strongly label human brain cancers associated with disrupted blood-brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs)...
September 6, 2016: Molecular Pharmaceutics
Shijun Hu, Ming-Tao Zhao, Fereshteh Jahanbani, Ning-Yi Shao, Won Hee Lee, Haodong Chen, Michael P Snyder, Joseph C Wu
Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC-derived ECs...
June 2, 2016: JCI Insight
Javier Linares, Estibaliz Arellano-Viera, Olalla Iglesias-García, Carmen Ferreira, Elena Iglesias, Gloria Abizanda, Felipe Prósper, Xonia Carvajal-Vergara
Mef2c Anterior Heart Field (AHF) enhancer is activated during embryonic heart development and it is expressed in multipotent cardiovascular progenitors (CVP) giving rise to endothelial and myocardial components of the outflow tract, right ventricle and ventricular septum. Here we have generated iPSC from transgenic Mef2c-AHF-Cre x Ai6(RCLZsGreen) mice. These iPSC will provide a novel tool to investigate the AHF-CVP and their cell progeny.
May 2016: Stem Cell Research
Hasan E Abaci, Zongyou Guo, Abigail Coffman, Brian Gillette, Wen-Han Lee, Samuel K Sia, Angela M Christiano
Vascularization of engineered human skin constructs is crucial for recapitulation of systemic drug delivery and for their long-term survival, functionality, and viable engraftment. In this study, the latest microfabrication techniques are used and a novel bioengineering approach is established to micropattern spatially controlled and perfusable vascular networks in 3D human skin equivalents using both primary and induced pluripotent stem cell (iPSC)-derived endothelial cells. Using 3D printing technology makes it possible to control the geometry of the micropatterned vascular networks...
July 2016: Advanced Healthcare Materials
Qizhou Lian, Yuelin Zhang, Xiaoting Liang, Fei Gao, Hung-Fat Tse
Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days...
2016: Methods in Molecular Biology
Vasiliy Galat, Yekaterina Galat, Mariana Perepitchka, Lawrence J Jennings, Philip M Iannaccone, Mary J C Hendrix
Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc...
July 15, 2016: Stem Cells and Development
David G Belair, Michael P Schwartz, Thomas Knudsen, William L Murphy
UNLABELLED: Activation of vascular endothelial cells (ECs) by growth factors initiates a cascade of events during angiogenesis in vivo consisting of EC tip cell selection, sprout formation, EC stalk cell proliferation, and ultimately vascular stabilization by support cells. Although EC functional assays can recapitulate one or more aspects of angiogenesis in vitro, they are often limited by undefined substrates and lack of dependence on key angiogenic signaling axes. Here, we designed and characterized a chemically-defined model of endothelial sprouting behavior in vitro using human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs)...
July 15, 2016: Acta Biomaterialia
Moriah E Katt, Zinnia S Xu, Sharon Gerecht, Peter C Searson
The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial cells (hBMECs) from human induced pluripotent stem cells (iPSCs) may provide a solution to this problem...
2016: PloS One
Ronak Patel, Abraham J Alahmad
BACKGROUND: Patient-derived induced pluripotent stem cells (iPSCs) are an innovative source as an in vitro model for neurological diseases. Recent studies have demonstrated the differentiation of brain microvascular endothelial cells (BMECs) from various stem cell sources, including iPSC lines. However, the impact of the culturing conditions used to maintain such stem cell pluripotency on their ability to differentiate into BMECs remains undocumented. In this study, we investigated the effect of different sources of Matrigel and stem cell maintenance medium on BMEC differentiation efficiency...
2016: Fluids and Barriers of the CNS
Oriane Guillevic, Ségolène Ferratge, Juliette Pascaud, Catherine Driancourt, Julie Boyer-Di-Ponio, Georges Uzan
Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies...
2016: PloS One
Peggy Matz, James Adjaye
Human umbilical vein endothelial cells (HUVECs) were used to generate the iPSC line epiHUVEC employing a combination of three episomal-based plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and KLF4. Pluripotency was confirmed both in vivo and in vitro. The transcriptome profile of epiHUVEC and the human embryonic stem cell line - H1 have a Pearson correlation of 0.899.
November 2015: Stem Cell Research
Matthew R Zanotelli, Hamisha Ardalani, Jue Zhang, Zhonggang Hou, Eric H Nguyen, Scott Swanson, Bao Kim Nguyen, Jennifer Bolin, Angela Elwell, Lauren L Bischel, Angela W Xie, Ron Stewart, David J Beebe, James A Thomson, Michael P Schwartz, William L Murphy
UNLABELLED: Here, we describe an in vitro strategy to model vascular morphogenesis where human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) are encapsulated in peptide-functionalized poly(ethylene glycol) (PEG) hydrogels, either on standard well plates or within a passive pumping polydimethylsiloxane (PDMS) tri-channel microfluidic device. PEG hydrogels permissive towards cellular remodeling were fabricated using thiol-ene photopolymerization to incorporate matrix metalloproteinase (MMP)-degradable crosslinks and CRGDS cell adhesion peptide...
April 15, 2016: Acta Biomaterialia
Muhammad Z Afzal, Melanie Reiter, Courtney Gastonguay, Jered V McGivern, Xuan Guan, Zhi-Dong Ge, David L Mack, Martin K Childers, Allison D Ebert, Jennifer L Strande
BACKGROUND: Dystrophin-deficient cardiomyopathy is a growing clinical problem without targeted treatments. We investigated whether nicorandil promotes cardioprotection in human dystrophin-deficient induced pluripotent stem cell (iPSC)-derived cardiomyocytes and the muscular dystrophy mdx mouse heart. METHODS AND RESULTS: Dystrophin-deficient iPSC-derived cardiomyocytes had decreased levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase. The dystrophin-deficient cardiomyocytes had increased cell injury and death after 2 hours of stress and recovery...
March 2, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
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