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https://www.readbyqxmd.com/read/28286868/a-basis-for-comparison-sensitive-authentication-of-stem-cell-derived-rpe-using-physiological-responses-of-intact-rpe-monolayers
#1
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
#2
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
https://www.readbyqxmd.com/read/28275009/paracrine-signals-regulate-human-liver-organoid-maturation-from-ipsc
#3
Akihiro Asai, Eitaro Aihara, Carey Watson, Reena Mourya, Tatsuki Mizuochi, Pranavkumar Shivakumar, Kieran Phelan, Christopher Mayhew, Michael Helmrath, Takanori Takebe, James Wells, Jorge A Bezerra
A self-organizing organoid model provides a new approach to study the mechanism of human liver organogenesis. Previous animal models documented that simultaneous paracrine signaling and cell-to-cell surface contact regulate hepatocyte differentiation. To dissect the relative contributions of the paracrine effects, we first established a liver organoid using human induced pluripotent stem cells (iPSC), mesenchymal stem cells (MSC), and human umbilical vein endothelial cells (HUVEC) as previously reported. Time-lapse imaging showed the iPSC-derived hepatic endoderm (HE-iPSC) self-assembled into three-dimensional organoids, resulting in hepatic gene induction...
March 8, 2017: Development
https://www.readbyqxmd.com/read/28238797/in%C3%A2-vitro-modeling-of-blood-brain-barrier-with-human-ipsc-derived-endothelial-cells-pericytes-neurons-and-astrocytes-via-notch-signaling
#4
Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K Yamashita
The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells (BECs), pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs) were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A) and efflux transporters (ABCA1, BCRP, PGP, MRP5), and strong barrier function based on tight junctions...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28209385/a-comparison-of-the-pro-angiogenic-potential-of-human-induced-pluripotent-stem-cell-derived-endothelial-cells-and-induced-endothelial-cells-in-a-murine-model-of-peripheral-arterial-disease
#5
Zoe E Clayton, Gloria S C Yuen, Sara Sadeghipour, Jack D Hywood, Jack W T Wong, Ngan F Huang, Martin K C Ng, John P Cooke, Sanjay Patel
BACKGROUND: Endothelial cells derived from human induced pluripotent stem cells (iPSC-ECs) promote angiogenesis, and more recently induced endothelial cells (iECs) have been generated via fibroblast trans-differentiation. These cell types have potential as treatments for peripheral arterial disease (PAD). However, it is unknown whether different reprogramming methods produce cells that are equivalent in terms of their pro-angiogenic capabilities. OBJECTIVES: We aimed to directly compare iPSC-ECs and iECs in an animal model of PAD, in order to identify which cell type, if any, displays superior therapeutic potential...
May 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28191018/thymosin-%C3%AE-4-improves-differentiation-and-vascularization-of-ehts
#6
Tilman Ziegler, Rabea Hinkel, Andrea Stöhr, Thomas Eschenhagen, Karl-Ludwig Laugwitz, Ferdinand le Noble, Robert David, Arne Hansen, Christian Kupatt
Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28069694/myocardial-tissue-engineering-with-cells-derived-from-human-induced-pluripotent-stem-cells-and-a-native-like-high-resolution-3-dimensionally-printed-scaffold
#7
Ling Gao, Molly Kupfer, Jangwook Jung, Libang Yang, Patrick Zhang, Yong Sie, Quyen Tran, Visar Ajeti, Brian Freeman, Vladimir Fast, Paul Campagnola, Brenda Ogle, Jianyi Zhang
RATIONALE: Conventional three-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact. OBJECTIVE: Here, we used multiphoton-excited, 3-dimensional printing (MPE-3DP) to generate a native-like, extracellular matrix (ECM) scaffold with submicron resolution, and then seeded the scaffold with cardiomyocytes (CMs), smooth-muscle cells (SMCs), and endothelial cells (ECs) that had been differentiated from human induced-pluripotent stem cells (iPSCs) to generate a human, iPSC-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction (MI)...
January 9, 2017: Circulation Research
https://www.readbyqxmd.com/read/28017794/patient-specific-ipsc-derived-endothelial-cells-uncover-pathways-that-protect-against-pulmonary-hypertension-in-bmpr2-mutation-carriers
#8
Mingxia Gu, Ning-Yi Shao, Silin Sa, Dan Li, Vittavat Termglinchan, Mohamed Ameen, Ioannis Karakikes, Gustavo Sosa, Fabian Grubert, Jaecheol Lee, Aiqin Cao, Shalina Taylor, Yu Ma, Zhixin Zhao, James Chappell, Rizwan Hamid, Eric D Austin, Joseph D Gold, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch
In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls to investigate this variation. Our analysis identified features of UMC iPSC-ECs related to modifiers of BMPR2 signaling or to differentially expressed genes...
December 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28000095/exosomes-from-ipscs-delivering-sirna-attenuate-intracellular-adhesion-molecule-1-expression-and-neutrophils-adhesion-in-pulmonary-microvascular-endothelial-cells
#9
Zhihai Ju, Jinhui Ma, Chen Wang, Jie Yu, Yeru Qiao, Feilong Hei
The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine...
April 2017: Inflammation
https://www.readbyqxmd.com/read/27965171/human-placenta-hydrogel-reduces-scarring-in-a-rat-model-of-cardiac-ischemia-and-enhances-cardiomyocyte-and-stem-cell-cultures
#10
Michael P Francis, Erick Breathwaite, Anna A Bulysheva, Frency Varghese, Rudy U Rodriguez, Sucharita Dutta, Iurii Semenov, Rebecca Ogle, Alexander Huber, Alexandra-Madelaine Tichy, Silvia Chen, Christian Zemlin
INTRODUCTION: Xenogeneic extracellular matrix (ECM) hydrogels have shown promise in remediating cardiac ischemia damage in animal models, yet analogous human ECM hydrogels have not been well development. An original human placenta-derived hydrogel (hpECM) preparation was thus generated for assessment in cardiomyocyte cell culture and therapeutic cardiac injection applications. METHODS AND RESULTS: Hybrid orbitrap-quadrupole mass spectrometry and ELISAs showed hpECM to be rich in collagens, basement membrane proteins, and regenerative growth factors (e...
December 10, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27938475/imbalanced-production-of-reactive-oxygen-species-and-mitochondrial-antioxidant-sod2-in-fabry-disease-specific-human-induced-pluripotent-stem-cell-differentiated-vascular-endothelial-cells
#11
Wei-Lien Tseng, Shih-Jie Chou, Huai-Chih Chiang, Mong-Lien Wang, Chian-Shiu Chien, Kuan-Hsuan Chen, Hsin-Bang Leu, Chien-Ying Wang, Yuh-Lih Chang, Yung-Yang Liu, Yuh-Jyh Jong, Shinn-Zong Lin, Shih-Hwa Chiou, Shing-Jong Lin, Wen-Chung Yu
Fabry disease (FD) is an X-linked inherited lysosomal storage disease caused by α-galactosidase A (GLA) deficiency. Progressive intracellular accumulation of globotriaosylceramide (Gb3) is considered to be pathogenically responsible for the phenotype variability of FD that causes cardiovascular dysfunction; however, molecular mechanisms underlying the impairment of FD-associated cardiovascular tissues remain unclear. In this study, we reprogrammed human induced pluripotent stem cells (hiPSCs) from peripheral blood cells of patients with FD (FD-iPSCs); subsequently differentiated them into vascular endothelial-like cells (FD-ECs) expressing CD31, VE-cadherin, and vWF; and investigated their ability to form vascular tube-like structures...
March 13, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/27935037/an-isogenic-blood-brain-barrier-model-comprising-brain-endothelial-cells-astrocytes-and-neurons-derived-from-human-induced-pluripotent-stem-cells
#12
Scott G Canfield, Matthew J Stebbins, Bethsymarie Soto Morales, Shusaku W Asai, Gad D Vatine, Clive N Svendsen, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation...
March 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27888517/differentiation-of-induced-pluripotent-stem-cell-derived-neutrophil-granulocytes-from-common-marmoset-monkey-callithrix-jacchus
#13
Christopher Schrimpf, Christoph Wrede, Silke Glage, Jan Hegermann, Samantha Backhaus, Rainer Blasczyk, Hans-Gert Heuft, Thomas Müller
BACKGROUND: Inherited and acquired marrow failure syndromes most commonly lead to defect in myeloid and/or neutrophil differentiation and/or function. Besides this, neutropenia induced by cancer-adjusted chemotherapy is a frequent clinical problem. In both cases, cell replacement therapy is a well-established, but due to necessity of donors limited and perilous procedure. Therefore, autologous cell replacement from patients' own marrow-derived cells lowers risk and bares new possibilities for therapy...
January 2017: Transfusion
https://www.readbyqxmd.com/read/27867156/transcriptional-analysis-of-intravenous-immunoglobulin-resistance-in-kawasaki-disease-using-an-induced-pluripotent-stem-cell-disease-model
#14
Kazuyuki Ikeda, Yasutaka Mizoro, Tomonaga Ameku, Yui Nomiya, Shin-Ichi Mae, Satoshi Matsui, Yuki Kuchitsu, Chinatsu Suzuki, Akiko Hamaoka-Okamoto, Tomoyo Yahata, Masakatsu Sone, Keisuke Okita, Akira Watanabe, Kenji Osafune, Kenji Hamaoka
BACKGROUND: Approximately 10-20% of Kawasaki disease (KD) patients are resistant to intravenous immunoglobulin (IVIG) treatment. Further, these patients are at a particularly high risk of having coronary artery abnormalities. The mechanisms of IVIG resistance in KD have been analyzed using patient leukocytes, but not patient vascular endothelial cells (ECs). The present study clarifies the mechanisms of IVIG resistance in KD using an induced pluripotent stem cell (iPSC) disease model...
December 22, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27846787/cryopreservation-of-brain-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells-is-enhanced-by-rho-associated-coiled-coil-containing-kinase-inhibition
#15
Hannah K Wilson, Madeline G Faubion, Michael K Hjortness, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies...
December 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27779452/ipsc-model-of-pulmonary-arterial-hypertension-reveals-novel-gene-expression-and-patient-specificity
#16
Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch
RATIONALE: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology but different causal mechanisms may reflect a need for patient-tailored therapies. OBJECTIVES: Endothelial cells differentiated from induced pluripotent stem cells were compared to pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns, that differed from those in unused donor cells...
October 25, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27779219/establishment-of-a-translational-endothelial-cell-model-using-directed-differentiation-of-induced-pluripotent-stem-cells-from-cynomolgus-monkey
#17
Eva C Thoma, Tobias Heckel, David Keller, Nicolas Giroud, Brian Leonard, Klaus Christensen, Adrian Roth, Cristina Bertinetti-Lapatki, Martin Graf, Christoph Patsch
Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27731397/role-of-mir-155-in-controlling-hif-1%C3%AE-level-and-promoting-endothelial-cell-maturation
#18
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
https://www.readbyqxmd.com/read/27725898/ipsc-derived-cancer-stem-cells-provide-a-model-of-tumor-vasculature
#19
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
https://www.readbyqxmd.com/read/27662211/cellular-functions-and-gene-and-protein-expression-profiles-in-endothelial-cells-derived-from-moyamoya-disease-specific-ips-cells
#20
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
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