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https://www.readbyqxmd.com/read/30082272/tumor-stroma-interactions-differentially-alter-drug-sensitivity-based-on-the-origin-of-stromal-cells
#1
Benjamin D Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R Schwartz, Megan E Honeywell, Gary Ren, Alyssa D Schwartz, Shelly R Peyton, Michael J Lee
Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts...
August 6, 2018: Molecular Systems Biology
https://www.readbyqxmd.com/read/30072992/human-liver-stem-cell-derived-extracellular-vesicles-prevent-aristolochic-acid-induced-kidney-fibrosis
#2
Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
With limited therapeutic intervention in preventing the progression to end-stage renal disease, chronic kidney disease (CKD) remains a global health-care burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury, and interstitial fibrosis. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA-induced mouse model of CKD...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30065836/platelets-regulate-leucocyte-responses-to-toll-like-receptor-stimulation
#3
Kathryn E Hally, Anne C La Flamme, Scott A Harding, Peter D Larsen
Objectives: Platelets are important regulators of vascular thrombosis and inflammation and are known to express Toll-like receptors (TLRs). Through TLRs, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate in vitro peripheral blood mononuclear cells (PBMCs) and granulocyte responses to TLR4, TLR2/1 and TLR2/6 stimulation in healthy subjects. Methods: Peripheral blood mononuclear cells and granulocytes from 10 healthy volunteers were cultured alone or cocultured with platelets...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/30060947/human-gingival-fibroblast-feeder-cells-promote-maturation-of-induced-pluripotent-stem-cells-into-cardiomyocytes
#4
Yusuke Matsuda, Ken Takahashi, Hiroshi Kamioka, Keiji Naruse
The use of human induced pluripotent stem (iPS) cells has been investigated in multiple regenerative medicine studies. However, although methods for efficient differentiation of iPS cells into heart tissues have been devised, it remains difficult to obtain cardiac tissue with high contractility. Herein, we established a method for differentiating iPS cells into highly contractile cardiomyocytes (CMs), and demonstrate that the use of human gingival fibroblasts (HGFs) as a feeder cells promotes maturation of iPS-derived CMs (iPS-CMs) in vitro...
July 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30032862/c5l2-silencing-in-human-pulp-fibroblasts-enhances-nerve-outgrowth-under-lipoteichoic-acid-stimulation
#5
Fanny Chmilewsky, Imad About, Lyndon F Cooper, Seung H Chung
INTRODUCTION: We recently reported that caries-associated C5a receptor (C5aR) expression and activation result in up-regulation of brain-derived neurotropic factor secretion by pulp fibroblasts inducing prominent neurite outgrowth toward the carious site. Our data further showed a negative regulation of this brain-derived neurotropic factor secretion by C5L2, another C5aR. C5L2 was considered a nonfunctional receptor and thus has received much less attention than C5aR. The aim of this study was to identify the role of C5L2 in pulp fibroblast-mediated neurite outgrowth...
July 19, 2018: Journal of Endodontics
https://www.readbyqxmd.com/read/30019109/expression-kinetics-of-human-periodontal-ligament-fibroblasts-in-the-early-phases-of-orthodontic-tooth-movement
#6
Agnes Schröder, Kathrin Bauer, Gerrit Spanier, Peter Proff, Michael Wolf, Christian Kirschneck
PURPOSE: Human periodontal ligament (hPDL) fibroblasts play a crucial mediating role in orthodontic tooth movement (OTM). In this study, we investigated the expression kinetics of genes associated with OTM in its early phase to obtain better insight into the timing and regulation of molecular and cellular signalling and transformation processes occurring in compressive areas of the periodontal ligament during OTM. METHODS: Adherent hPDL fibroblasts were stimulated with physiological orthodontic compressive forces of 2 g/cm2 for 24, 48, 72, and 96 h under cell culture conditions...
July 17, 2018: Journal of Orofacial Orthopedics, Fortschritte der Kieferorthopädie
https://www.readbyqxmd.com/read/29915432/%C3%AF-editors-choice%C3%AF-effects-of-exosomes-derived-from-the-induced-pluripotent-stem-cells-on-skin-wound-healing
#7
Hitoshi Kobayashi, Katsumi Ebisawa, Miki Kambe, Takatoshi Kasai, Hidetaka Suga, Kae Nakamura, Yuji Narita, Aika Ogata, Yuzuru Kamei
Recently, the effects of stem cell supernatants or exosomes, such as skin wounds, have attracted attention. However, the effects of the induced pluripotent stem (iPS) cell-derived exosomes (iPS-Exos) have not been investigated in detail. Here, we investigated the effects of iPS-Exos on skin wound healing using an animal model. We isolated iPS-Exos from the iPS cell culture media. Control exosomes were isolated from unused iPS cell culture media (M-Exos). We first observed the morphologic characteristics of the isolated exosomes and examined the expression of surface antigens...
May 2018: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/29910803/expression-of-programmed-death-ligand-1-by-human-colonic-cd90-stromal-cells-differs-between-ulcerative-colitis-and-crohn-s-disease-and-determines-their-capacity-to-suppress-th1-cells
#8
Ellen J Beswick, Carl Grim, Abinav Singh, Jose E Aguirre, Marissa Tafoya, Suimin Qiu, Gerhard Rogler, Rohini McKee, Von Samedi, Thomas Y Ma, Victor E Reyes, Don W Powell, Irina V Pinchuk
Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29901432/host-pathogen-interaction-reconstituted-in-three-dimensional-cocultures-of-mucosa-and-candida-albicans
#9
Romina Buchs, Bruno Lehner, Philippe Meuwly, Bruno Schnyder
Candida albicans frequently causes recurrent intimal infectious disease (ID). This demands the treatment of multiple phases of the infection. The objective of this study was to uncover the host-pathogen interaction using two-dimensional (2D) epithelium cell-barrier and three-dimensional (3D) subepithelium tissue cells of human mucosa. The 2D cell cultures assessed C. albicans adhesion. Addition of the antifungal drug Fluconazol did not inhibit the adhesion, despite its pathogen growth inhibition (minimal inhibitory concentration value 0...
July 2018: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29898959/myeloid-cell-restricted-stat3-signaling-controls-a-cell-autonomous-antifibrotic-repair-program
#10
Nhu-Nguyen Do, Sebastian Willenborg, Beate Eckes, Christian Jüngst, Gerhard Sengle, Frank Zaucke, Sabine A Eming
Myeloid cells can be beneficial as well as harmful in tissue regenerative responses. The molecular mechanisms by which myeloid cells control this critical decision of the immune system are not well understood. Using two different models of physiological acute or pathological chronic skin damage, in this study we identified myeloid cell-restricted STAT3 signaling as important and an injury context-dependent regulator of skin fibrosis. Targeted disruption of STAT3 signaling in myeloid cells significantly accelerated development of pathological skin fibrosis in a model of chronic bleomycin-induced tissue injury, whereas the impact on wound closure dynamics and quality of healing after acute excision skin injury was minor...
July 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29876540/spatial-and-temporal-confined-photothermolysis-of-cancer-cells-mediated-by-hollow-gold-nanospheres-targeted-to-epidermal-growth-factor-receptors
#11
Geng Ku, Qian Huang, Xiaoxia Wen, John Ye, David Piwnica-Worms, Chun Li
To date, a few studies have investigated the potential use of a short-pulsed laser in selective tumor cell destruction or its mechanism of cell killing. Computer simulation of the spatial and temporal profiles of temperature elevation after pulsed laser irradiation on an infinitesimal point source estimated that the temperature reached its highest point at ∼35 ns after a single 15 ns laser pulse. Moreover, temperature elevation was confined to a radius of sub-micrometer and returned to baseline within 100 ns...
May 31, 2018: ACS Omega
https://www.readbyqxmd.com/read/29863945/roles-of-the-clec-2-podoplanin-interaction-in-tumor-progression
#12
Katsue Suzuki-Inoue
Podoplanin is a type-I transmembrane sialomucin-like glycoprotein expressed on the surface of several kinds of tumor cells. The podoplanin receptor is a platelet activation receptor known as C-type lectin-like receptor 2 (CLEC-2), which has been identified as a receptor for the platelet-activating snake venom protein rhodocytin. CLEC-2 is highly expressed in platelets and megakaryocytes and expressed at lower levels in liver Kupffer cells. Podoplanin is expressed in certain types of tumor cells, including squamous cell carcinomas, seminomas, and brain tumors...
June 4, 2018: Platelets
https://www.readbyqxmd.com/read/29798932/high-throughput-fabrication-of-vascularized-spheroids-for-bioprinting
#13
Lise De Moor, Idriz Merovci, Sarah Baetens, Julien Verstraeten, Paulina Kowalska, Dmitri V Krysko, Winnok H De Vos, Heidi Declercq
Overcoming the problem of vascularization remains the main challenge in the field of tissue engineering. As three-dimensional (3D) bioprinting is the rising technique for the fabrication of large tissue constructs, small prevascularized building blocks were generated that can be incorporated throughout a printed construct, answering the need for a microvasculature within the small micron range (<10 μm). Uniform spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system...
June 12, 2018: Biofabrication
https://www.readbyqxmd.com/read/29737948/heat-stress-and-hepatic-laser-thermal-ablation-induce-hepatocellular-carcinoma-growth-role-of-pi3k-mtor-akt-signaling
#14
Danielle E Jondal, Scott M Thompson, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Rickey E Carter, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group)...
May 8, 2018: Radiology
https://www.readbyqxmd.com/read/29726981/dickkopf-3-in-aberrant-endothelial-secretome-triggers-renal-fibroblast-activation-and-endothelial-mesenchymal-transition
#15
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29665133/isolation-of-a-unique-hepatic-stellate-cell-population-expressing-integrin-%C3%AE-8-from-embryonic-mouse-livers
#16
Tomohiro Ogawa, Yuchang Li, Ingrid Lua, Andrea Hartner, Kinji Asahina
BACKGROUND: Hepatic stellate cells (HSCs) play an important role in liver fibrogenesis. However, little is known about their phenotype and role in liver development. The aim of this study is to identify specific markers for embryonic HSCs. RESULTS: Using antibodies against ALCAM and PDPN, we separated mesothelial cells (MCs) and HSCs from developing livers and identified integrin α8 (ITGA8) as a marker for embryonic desmin+ HSCs that are preferentially localized near the developing liver surface and α-smooth muscle actin+ perivascular mesenchymal cells around the vein...
June 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29658964/micropassage-embedding-composite-hydrogel-fibers-enable-quantitative-evaluation-of-cancer-cell-invasion-under-3d-coculture-conditions
#17
Manami Sugimoto, Yoichi Kitagawa, Masumi Yamada, Yuya Yajima, Rie Utoh, Minoru Seki
Cell migration and invasion are of significant importance in physiological phenomena, including wound healing and cancer metastasis. Here we propose a new system for quantitatively evaluating cancer cell invasion in a three-dimensional (3D), in vivo tissue-like environment. This system uses composite hydrogel microfibers whose cross section has a relatively soft micropassage region and that were prepared using a multilayered microfluidic device; cancer cells are encapsulated in the core and fibroblasts are seeded in the shell regions surrounding the core...
May 1, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29625470/human-conjunctival-epithelial-sheets-grown-on-poly-lactic-co-glycolic-acid-membranes-and-cocultured-with-human-tenon-s-fibroblasts-for-corneal-repair
#18
Soyoung Hong, Je Hwan Yun, Eun-Soon Kim, Ji Seon Kim, Hungwon Tchah, Changmo Hwang
Purpose: We determine the feasibility of human conjunctival epithelial cells (hCjECs) on poly(lactic-co-glycolic) acid (PLGA) membranes for corneal epithelium regeneration. hCjECs on PLGA or polyester (PET) membranes with or without coculture of human Tenon's fibroblasts (hTFs) were compared in vitro, and to determine whether epithelial sheets grown on PLGA membranes can repair injured rabbit corneal epithelium by transplantation for 2 weeks in vivo. Methods: Primary hCjECs were cultured on PLGA or the original PET membrane-based transwell inserts with or without coculture of hTFs on the floor of the culture plate...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29619372/irradiated-human-umbilical-vein-endothelial-cells-undergo-endothelial-mesenchymal-transition-via-the-snail-mir-199a-5p-axis-to-promote-the-differentiation-of-fibroblasts-into-myofibroblasts
#19
Minxiao Yi, Bo Liu, Yang Tang, Fang Li, Wan Qin, Xianglin Yuan
Radiation induced pulmonary fibrosis (RIPF) is one of the major side effects of radiotherapy for lung cancer. Previous studies have shown that endothelial cells and activated myofibroblasts play a key role in RIPF. However, the interaction between irradiated endothelial cells and activation of myofibroblasts has not been reported. The aim of the present study was to examine whether irradiated endothelial cells would affect the differentiation of fibroblasts into myofibroblasts in the process of RIPF. In the current study, we used a coculture system that allowed direct contact between human fetal lung fibroblasts (MRC-5) and irradiated human umbilical vein endothelial cells (HUVECs)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29507627/cancer-associated-fibroblasts-enhance-tumor-18-f-fdg-uptake-and-contribute-to-the-intratumor-heterogeneity-of-pet-ct
#20
Chengfang Shangguan, Guifang Gan, Jieying Zhang, Jinliang Wu, Ying Miao, Miao Zhang, Biao Li, Jun Mi
Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent 18 F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low)...
2018: Theranostics
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