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https://www.readbyqxmd.com/read/28333915/directed-differentiation-of-human-induced-pluripotent-stem-cells-into-functional-cholangiocyte-like-cells
#1
Fotios Sampaziotis, Miguel Cardoso de Brito, Imbisaat Geti, Alessandro Bertero, Nicholas Rf Hannan, Ludovic Vallier
The difficulty in isolating and propagating functional primary cholangiocytes is a major limitation in the study of biliary disorders and the testing of novel therapeutic agents. To overcome this problem, we have developed a platform for the differentiation of human pluripotent stem cells (hPSCs) into functional cholangiocyte-like cells (CLCs). We have previously reported that our 26-d protocol closely recapitulates key stages of biliary development, starting with the differentiation of hPSCs into endoderm and subsequently into foregut progenitor (FP) cells, followed by the generation of hepatoblasts (HBs), cholangiocyte progenitors (CPs) expressing early biliary markers and mature CLCs displaying cholangiocyte functionality...
April 2017: Nature Protocols
https://www.readbyqxmd.com/read/28330898/antigen-presenting-human-%C3%AE-%C3%AE-t-cells-promote-intestinal-cd4-t-cell-expression-of-il-22-and-mucosal-release-of-calprotectin
#2
Christopher J Tyler, Neil E McCarthy, James O Lindsay, Andrew J Stagg, Bernhard Moser, Matthias Eberl
The cytokine IL-22 plays a critical role in mucosal barrier defense, but the mechanisms that promote IL-22 expression in the human intestine remain poorly understood. As human microbe-responsive Vγ9/Vδ2 T cells are abundant in the gut and recognize microbiota-associated metabolites, we assessed their potential to induce IL-22 expression by intestinal CD4(+) T cells. Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4(+) T cells obtained from human blood or the colon...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28329001/experimental-demonstration-of-the-possible-role-of-acanthamoeba-polyphaga-in-the-infection-and-disease-progression-in-buruli-ulcer-bu-using-icr-mice
#3
Bright K Azumah, Phyllis G Addo, Alfred Dodoo, Gordon Awandare, Lydia Mosi, Daniel A Boakye, Michael D Wilson
The transmission of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), remains puzzling although a number of hypothesis including through bites of infected aquatic insects have been proposed. We report the results of experiments using ICR mice that give credence to our hypothesis that Acanthamoeba species may play a role in BU transmission. We cocultured MU N2 and MU 1615 which expresses red fluorescent protein (RFP) and Acanthamoeba polyphaga (AP), and confirmed infected AP by Ziehl-Neelsen (ZN) staining...
2017: PloS One
https://www.readbyqxmd.com/read/28326781/the-berkeleylactones-antibiotic-macrolides-from-fungal-coculture
#4
Andrea A Stierle, Donald B Stierle, Daniel Decato, Nigel D Priestley, Jeremy B Alverson, John Hoody, Kelly McGrath, Dorota Klepacki
A carefully timed coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones A-H (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide A26771B (5), patulin, and citrinin. There was no evidence of the production of the berkeleylactones or A26771B (5) by either fungus when grown as axenic cultures. The structures were deduced from analyses of spectral data, and the absolute configurations of compounds 1 and 9 were determined by single-crystal X-ray crystallography...
March 22, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28326081/the-smac-mimetic-bv6-improves-nk-cell-mediated-killing-of-rhabdomyosarcoma-cells-by-simultaneously-targeting-tumor-and-effector-cells
#5
Kyra Fischer, Sara Tognarelli, Stefanie Roesler, Cathinka Boedicker, Ralf Schubert, Alexander Steinle, Thomas Klingebiel, Peter Bader, Simone Fulda, Evelyn Ullrich
Rhabdomyosarcoma (RMS), the most common cancer of connective tissues in pediatrics, is often resistant to conventional therapies. One underlying mechanism of this resistance is the overexpression of Inhibitor of Apoptosis (IAP) proteins, leading to a dysfunctional cell death program within tumor cells. Smac mimetics (SM) are small molecules that can reactivate the cell death program by antagonizing IAP proteins and thereby compensating their overexpression. Here, we report that SM sensitize two RMS cell lines (RD and RH30) toward natural killer (NK) cell-mediated killing on the one hand, and increase the cytotoxic potential of NK cells on the other...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325763/pseudomonas-aeruginosa-alginate-overproduction-promotes-coexistence-with-staphylococcus-aureus-in-a-model-of-cystic-fibrosis-respiratory-infection
#6
Dominique H Limoli, Gregory B Whitfield, Tomoe Kitao, Melissa L Ivey, Michael R Davis, Nora Grahl, Deborah A Hogan, Laurence G Rahme, P Lynne Howell, George A O'Toole, Joanna B Goldberg
While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28322015/compartmentalized-spherical-collagen-microparticles-for-anisotropic-cell-culture-microenvironments
#7
Satoru Yoshida, Masahiro Takinoue, Hiroaki Onoe
This paper describes a new fabrication method for obtaining anisotropic spherical hydrogel microparticles with different types of extracellular matrix (ECM) hemispheres for use in 3D cell culture. To fabricate the microparticles, a mixture of an ECM precursor solution and sodium alginate is ejected into a calcium chloride solution under large centrifugal acceleration by a centrifuge-based microfluidic device; the calcium alginate hydrogel plays a significant role as a "sacrificial gelation template" to maintain the ECM molecules in each hemisphere...
March 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28320829/tissue-engineering-functional-gastrointestinal-regions-the-importance-of-stem-and-progenitor-cells
#8
Andrew Trecartin, Tracy Grikscheit
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28316601/the-interplay-between-radioresistant-caco-2-cells-and-the-immune-system-increases-epithelial-layer-permeability-and-alters-signaling-protein-spectrum
#9
Jacopo Morini, Gabriele Babini, Sofia Barbieri, Giorgio Baiocco, Andrea Ottolenghi
Colorectal cancer is one of the most frequent type of cancer, with a higher incidence in the developed countries. Colorectal cancer is usually managed with both surgeries, chemotherapy and radiotherapy. Radiotherapy has the well-known advantage of targeting the tumor, minimizing normal tissue exposure. Nevertheless, during radiation treatment, exposure of healthy tissues is of great concern, in particular because of the effects on the intestinal barrier functions and on cells belonging to the immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28303245/biocompatibility-and-effectiveness-evaluation-of-a-new-hemostatic-embolization-agent-thrombin-loaded-alginate-calcium-microsphere
#10
Fengqi Xuan, Jingjing Rong, Ming Liang, Xuwen Zhang, Jingyang Sun, Lijun Zhao, Yang Li, Dan Liu, Fei Li, Xiaozeng Wang, Yaling Han
Background. Until now, there has been no ideal embolization agent for hemorrhage in interventional treatment. In this study, the thrombin was encapsulated in alginate calcium microsphere using electrostatic droplet technique to produce new embolization agent: thrombin loaded alginate calcium microspheres (TACMs). Objectives. The present work was to evaluate the biocompatibility and hemostatic efficiency of TACMs. Methods. Cell cytotoxicity, hemolysis, and superselective embolization of dog liver arteries were performed to investigate the biocompatibility of TACMs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#11
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28299330/erythropoietin-modification-enhances-the-protection-of-mesenchymal-stem-cells-on-diabetic-rat-derived-schwann-cells-implications-for-diabetic-neuropathy
#12
Shuyun Zhang, Baolin Shi
Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28297582/human-stem-cell-derived-endothelial-hepatic-platform-for-efficacy-testing-of-vascular-protective-metabolites-from-nutraceuticals
#13
Balakrishnan Chakrapani Narmada, Yeek Teck Goh, Huan Li, Sanjay Sinha, Hanry Yu, Christine Cheung
Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#14
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28293065/the-combination-of-mbp-and-bcg-induced-dendritic-cell-maturation-through-tlr2-tlr4-promotes-th1-activation-in-vitro-and-vivo
#15
LiNa Jiang, GuoMu Liu, WeiHua Ni, NanNan Zhang, Jing Jie, Fei Xie, GuiXiang Tai
To explore whether TLR2/TLR4 could be involved in the maturation of dendritic cells and polarization of CD4(+) T cells induced by dendritic cells stimulated with MBP and BCG, in vitro and in vivo experiments using TLR2(-/-) or TLR4(-/-) mice were employed. MBP and BCG elevated CD80, CD86 and MHC class II expressed on dendritic cells and increased IL-12 protein, induced DC maturation, and indirectly promoted Th1 activation. Moreover, MBP and BCG upregulated costimulatory molecules on DCs in a TLR2- and TLR4-dependent manner...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28292959/multiepitope-tissue-analysis-reveals-sppl3-mediated-adam10-activation-as-a-key-step-in-the-transformation-of-melanocytes
#16
Christian Ostalecki, Jung-Hyun Lee, Jochen Dindorf, Lena Collenburg, Stephan Schierer, Beate Simon, Stefan Schliep, Elisabeth Kremmer, Gerold Schuler, Andreas S Baur
The evolution of cancer is characterized by the appearance of specific mutations, but these mutations are translated into proteins that must cooperate to induce malignant transformation. Using a systemic approach with the multiepitope ligand cartography (MELC) technology, we analyzed protein expression profiles (PEPs) in nevi and BRAF(V600E)-positive superficial spreading melanomas (SSMs) from patient tissues to identify key transformation events. The PEPs in nevi and SSMs differed predominantly in the abundance of specific antigens, but the PEPs of nevi- and melanoma-associated keratinocytes gradually changed during the transformation process...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#17
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28290290/mucus-interactions-with-liposomes-encapsulating-bioactives-interfacial-tensiometry-and-cellular-uptake-on-caco-2-and-cocultures-of-caco-2-ht29-mtx
#18
Yang Li, Elena Arranz, Anilda Guri, Milena Corredig
Structuring of delivery matrices in foods aquires careful designing for optimal delivery and subsiquent absorption of the beneficial compounds in the gut. There has been quite improvement in mimicking digestion and absorption in vitro but as of yet little is understood on mucus interference in nutrient absorption Therefore in this study interactions of human intestinal mucus with milk and soy phospholipids liposomes carring hydrophilic (epigallocatechin-3-gallate) or hydrophobic (β-carotene) bioactive molecules were investigated...
February 2017: Food Research International
https://www.readbyqxmd.com/read/28287607/mitoception-transferring-isolated-human-msc-mitochondria-to-glioblastoma-stem-cells
#19
Brice Nzigou Mombo, Sabine Gerbal-Chaloin, Aleksandra Bokus, Martine Daujat-Chavanieu, Christian Jorgensen, Jean-Philippe Hugnot, Marie-Luce Vignais
Mitochondria play a central role for cell metabolism, energy production and control of apoptosis. Inadequate mitochondrial function has been found responsible for very diverse diseases, ranging from neurological pathologies to cancer. Interestingly, mitochondria have recently been shown to display the capacity to be transferred between cell types, notably from human mesenchymal stem cells (MSC) to cancer cells in coculture conditions, with metabolic and functional consequences for the mitochondria recipient cells, further enhancing the current interest for the biological properties of these organelles...
February 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28287563/isolation-of-mouse-endometrial-epithelial-and-stromal-cells-for-in-vitro-decidualization
#20
Katrien De Clercq, Aurélie Hennes, Joris Vriens
Decidualization is a progesterone-dependent differentiation process of endometrial stromal cells and is a prerequisite for successful embryo implantation. Although many efforts have been made to reveal the underlying mechanisms of decidualization, the exact signaling between the epithelial cells that are in contact with the embryo and the underlying stromal cells remains poorly understood. Therefore, studying decidualization in a way that takes both the epithelial and stromal cells into account could improve our knowledge about the molecular details of decidualization...
March 2, 2017: Journal of Visualized Experiments: JoVE
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