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iPSc-derived endothelial

Moriah E Katt, Raleigh M Linville, Lakyn N Mayo, Zinnia S Xu, Peter C Searson
BACKGROUND: Transwell-based models of the blood-brain barrier (BBB) incorporating monolayers of human brain microvascular endothelial cells (dhBMECs) derived from induced pluripotent stem cells show many of the key features of the BBB, including expression of transporters and efflux pumps, expression of tight junction proteins, and physiological values of transendothelial electrical resistance. The fabrication of 3D BBB models using dhBMECs has so far been unsuccessful due to the poor adhesion and survival of these cells on matrix materials commonly used in tissue engineering...
February 20, 2018: Fluids and Barriers of the CNS
Dominique Manikowski, Birgit Andrée, Esther Samper, Clémence Saint-Marc, Ruth Olmer, Peter Vogt, Sarah Strauß, Axel Haverich, Andres Hilfiker
In natural tissues, the nutrition of cells and removal of waste products is facilitated by a dense capillary network which is generated during development. This perfusion system is also indispensable for tissue formation in vitro. Nutrition depending solely on diffusion is not sufficient to generate tissues of clinically relevant dimensions, which is a core aim in tissue engineering research. In this study, the establishment of a vascular network was investigated in a self-assembling approach employing endothelial and mural cells...
February 13, 2018: Vascular Pharmacology
Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K Yamashita
No abstract text is available yet for this article.
February 13, 2018: Stem Cell Reports
Jonathan R Bezenah, Yen P Kong, Andrew J Putnam
A major translational challenge in the fields of therapeutic angiogenesis and regenerative medicine is the need to create functional microvasculature. The purpose of this study was to assess whether a potentially autologous endothelial cell (EC) source derived from human induced pluripotent stem cells (iPSC-ECs) can form the same robust, stable microvasculature as previously documented for other sources of ECs. We utilized a well-established in vitro assay, in which endothelial cell-coated (iPSC-EC or HUVEC) beads were co-embedded with fibroblasts in a 3D fibrin matrix to assess their ability to form stable microvessels...
February 8, 2018: Scientific Reports
Nadia El Harane, Anaïs Kervadec, Valérie Bellamy, Laetitia Pidial, Hany J Neametalla, Marie-Cécile Perier, Bruna Lima Correa, Léa Thiébault, Nicolas Cagnard, Angéline Duché, Camille Brunaud, Mathilde Lemitre, Jeanne Gauthier, Alexandra T Bourdillon, Marc P Renault, Yeranuhi Hovhannisyan, Solenne Paiva, Alexandre R Colas, Onnik Agbulut, Albert Hagège, Jean-Sébastien Silvestre, Philippe Menasché, Nisa K E Renault
Aims: We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results: The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy...
February 6, 2018: European Heart Journal
Abbygail A Foster, Ruby E Dewi, Lei Cai, Luqia Hou, Zachary Strassberg, Cynthia A Alcazar, Sarah C Heilshorn, Ngan F Huang
A key feature of peripheral arterial disease (PAD) is damage to endothelial cells (ECs), resulting in lower limb pain and restricted blood flow. Recent preclinical studies demonstrate that the transplantation of ECs via direct injection into the affected limb can result in significantly improved blood circulation. Unfortunately, the clinical application of this therapy has been limited by low cell viability and poor cell function. To address these limitations we have developed an injectable, recombinant hydrogel, termed SHIELD (Shear-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery) for cell transplantation...
February 6, 2018: Biomaterials Science
Maria Ribecco-Lutkiewicz, Caroline Sodja, Julie Haukenfrers, Arsalan S Haqqani, Dao Ly, Peter Zachar, Ewa Baumann, Marguerite Ball, Jez Huang, Marina Rukhlova, Marzia Martina, Qing Liu, Danica Stanimirovic, Anna Jezierski, Mahmud Bani-Yaghoub
We have developed a renewable, scalable and transgene free human blood-brain barrier model, composed of brain endothelial cells (BECs), generated from human amniotic fluid derived induced pluripotent stem cells (AF-iPSC), which can also give rise to syngeneic neural cells of the neurovascular unit. These AF-iPSC-derived BECs (i-BEC) exhibited high transendothelial electrical resistance (up to 1500 Ω cm2) inducible by astrocyte-derived molecular cues and retinoic acid treatment, polarized expression of functional efflux transporters and receptor mediated transcytosis triggered by antibodies against specific receptors...
January 30, 2018: Scientific Reports
Patrick N Ingram, Laurel E Hind, Jose A Jiminez-Torres, Anna Huttenlocher, David J Beebe
While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)-derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model is demonstrated...
January 2018: Advanced Healthcare Materials
Ramona Weist, Thilo Flörkemeier, Yvonne Roger, Annika Franke, Kristin Schwanke, Robert Zweigerdt, Ulrich Martin, Elmar Willbold, Andrea Hoffmann
The components of the cholinergic system are evolutionary very old and conserved molecules that are expressed in typical spatiotemporal patterns. They are involved in signaling in the nervous system, whereas their functions in nonneuronal tissues are hardly understood. Stem cells present an attractive cellular system to address functional issues. This study therefore compared human induced pluripotent stem cells (iPSCs; from cord blood endothelial cells), mesenchymal stromal cells derived from iPSCs (iPSC-MSCs), and bone marrow-derived MSCs (BM-MSCs) from up to 33 different human donors with respect to gene expressions of components of the cholinergic system...
February 1, 2018: Stem Cells and Development
Ming-Tao Zhao, Haodong Chen, Qing Liu, Ning-Yi Shao, Nazish Sayed, Hung-Ta Wo, Joe Z Zhang, Sang-Ging Ong, Chun Liu, Youngkyun Kim, Huaxiao Yang, Tony Chour, Hong Ma, Nuria Marti Gutierrez, Ioannis Karakikes, Shoukhrat Mitalipov, Michael P Snyder, Joseph C Wu
Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular and functional features, and drug response of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically relevant sets of human iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro fertilization embryo-derived ESCs (IVF-ESCs)...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
Xiugong Gao, Jeffrey J Yourick, Robert L Sprando
Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs...
November 7, 2017: Stem Cell Research
Marta Adamiak, Guangming Cheng, Sylwia Bobis-Wozowicz, Lin Zhao, Sylwia Kedracka-Krok, Anweshan Samanta, Elzbieta Karnas, Yu-Ting Xuan, Bozena Skupien-Rabian, Xing Chen, Urszula Jankowska, Magdy Girgis, Malgorzata Sekula, Arash Davani, Slawomir Lasota, Robert J Vincent, Michal Sarna, Kathy L Newell, Ou-Li Wang, Nathaniel Dudley, Zbigniew Madeja, Buddhadeb Dawn, Ewa K Zuba-Surma
RATIONALE: Extracellular vesicles (EVs) are tiny membrane-enclosed droplets released by cells through membrane budding or exocytosis. The myocardial reparative abilities of EVs derived from induced pluripotent stem cells (iPSCs) have not been directly compared with the source iPSCs. OBJECTIVE: To examine whether iPSC-derived EVs can influence the biological functions of cardiac cells in vitro and to compare the safety and efficacy of iPSC-derived EVs (iPSC-EVs) and iPSCs for cardiac repair in vivo...
January 19, 2018: Circulation Research
Brandon J Kim, Olivia B Bee, Maura A McDonagh, Matthew J Stebbins, Sean P Palecek, Kelly S Doran, Eric V Shusta
Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with and penetrate the BBB to cause meningitis...
November 2017: MSphere
Hirokazu Narita, Fumiaki Shima, Junya Yokoyama, Shigeru Miyagawa, Yoshinari Tsukamoto, Yasushi Takamura, Ayami Hiura, Ken Fukumoto, Tomohiro Chiba, Seiji Watanabe, Yoshiki Sawa, Mitsuru Akashi, Hiroshi Shimoda
One of the major challenges in cell-based cardiac regenerative medicine is the in vitro construction of three-dimensional (3D) tissues consisting of induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) and a blood vascular network supplying nutrients and oxygen throughout the tissue after implantation. We have successfully built a vascularized iPSC-CM 3D-tissue using our validated cell manipulation technique. In order to evaluate an availability of the 3D-tissue as a biomaterial, functional morphology of the tissues was examined by light and transmission electron microscopy through their implantation into the rat infarcted heart...
October 20, 2017: Scientific Reports
Leni Moldovan, April Barnard, Chang-Hyun Gil, Yang Lin, Maria B Grant, Mervin C Yoder, Nutan Prasain, Nicanor I Moldovan
Recently a protocol is established to obtain large quantities of human induced pluripotent stem cells (iPSC)-derived endothelial progenitors, called endothelial colony forming cells (ECFC), and of candidate smooth-muscle forming cells (SMFC). Here, the suitability for assembling in spheroids, and in larger 3D cell constructs is tested. iPSC-derived ECFC and SMFC are labeled with tdTomato and eGFP, respectively. Spheroids are formed in ultra-low adhesive wells, and their dynamic proprieties are studied by time-lapse microscopy, or by confocal microscopy...
October 14, 2017: Biotechnology Journal
Yang Lin, Chang-Hyun Gil, Mervin C Yoder
The emergence of induced pluripotent stem cell (iPSC) technology paves the way to generate large numbers of patient-specific endothelial cells (ECs) that can be potentially delivered for regenerative medicine in patients with cardiovascular disease. In the last decade, numerous protocols that differentiate EC from iPSC have been developed by many groups. In this review, we will discuss several common strategies that have been optimized for human iPSC-EC differentiation and subsequent studies that have evaluated the potential of human iPSC-EC as a cell therapy or as a tool in disease modeling...
November 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Bin Xia, Yonggang Lv
Controlled delivery of multiple therapeutic agents can be considered an effective approach in nerve injury due to its multifunction. In this study, recombinant human vascular endothelial growth factor (VEGF) and recombinant human nerve growth factor (NGF) were loaded on the surface and in the core of emulsion electrospun poly (l-lactic acid) (PLLA) nanofibrous scaffold, respectively. The in vitro studies showed that VEGF and NGF had a sequential release pattern in which most of the VEFG was released in the first few days but the NGF could be continuously released for >1month...
January 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Rsituko Ohtani-Kaneko, Kenjiro Sato, Atsuhiro Tsutiya, Yuka Nakagawa, Kazutoshi Hashizume, Hidekatsu Tazawa
Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs)...
October 9, 2017: Biomedical Microdevices
Abraham J Al-Ahmad
Glucose constitutes a 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 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs)...
October 1, 2017: American Journal of Physiology. Cell Physiology
Matthew J Stebbins, Ethan S Lippmann, Madeline G Faubion, Richard Daneman, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) is critical to central nervous system (CNS) health. Brain microvascular endothelial cells (BMECs) are often used as in vitro BBB models for studying BBB dysfunction and therapeutic screening applications. Human pluripotent stem cells (hPSCs) can be differentiated to cells having key BMEC barrier and transporter properties, offering a renewable, scalable source of human BMECs. hPSC-derived BMECs have previously been shown to respond to all-trans retinoic acid (RA), and the goal of this study was to identify the stages at which differentiating human induced pluripotent stem cells (iPSCs) respond to activation of RA receptors (RARs) to impart BBB phenotypes...
September 28, 2017: Biotechnology Journal
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