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https://www.readbyqxmd.com/read/28813592/3d-printed-phema-materials-for-topographical-and-biochemical-modulation-of-dorsal-root-ganglion-cell-response
#1
Adina Badea, Joselle M McCracken, Emily G Tillmaand, Mikhail Eugene Kandel, Aaron W Oraham, Molly B Mevis, Stanislav S Rubakhin, Gabriel Popescu, Jonathan V Sweedler, Ralph G Nuzzo
Understanding and controlling the interactions occurring between cells and engineered materials are central challenges towards progress in the development of biomedical devices. In this work, we describe materials for direct ink writing (DIW), an extrusion-based type of 3D printing, that embed a custom synthetic protein (RGD-PDL) within the microfilaments of 3D-hydrogel scaffolds to modify these interactions and differentially direct tissue-level organization of complex cell populations in vitro. The RGD-PDL is synthesized by modifying poly-ᴅ-lysine (PDL) to varying extents with peptides containing the integrin-binding motif Arg-Gly-Asp (RGD)...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#2
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810923/the-chemokine-fractalkine-cx3cl1-attenuates-h2o2-induced-demyelination-in-cerebellar-slices
#3
Sinead A O'Sullivan, Kumlesh K Dev
BACKGROUND: Fractalkine/CX3CR1 signalling has been implicated in many neurodegenerative and neurological diseases of the central nervous system (CNS). This signalling pathway plays an important role in regulating reactive oxygen species (ROS), as well as itself being altered in conditions of oxidative stress. Here, we investigated the effects of recombinant fractalkine (rCX3CL1) in models of hydrogen peroxide (H2O2)-induced demyelination and astrocyte toxicity, within organotypic cerebellar slice cultures...
August 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28806855/functional-stem-cell-integration-into-neural-networks-assessed-by-organotypic-slice-cultures
#4
David Forsberg, Charoensri Thonabulsombat, Johan Jäderstad, Linda Maria Jäderstad, Petri Olivius, Eric Herlenius
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28806446/sema3a-reduces-sprouting-of-adult-rod-photoreceptors-in-vitro
#5
Frank Kung, Weiwei Wang, Tracy S Tran, Ellen Townes-Anderson
Purpose: Rod photoreceptor terminals respond to retinal injury with retraction and sprouting. Since the guidance cue Semaphorin3A (Sema3A) is observed in the retina after injury, we asked whether Sema3A contributes to structural plasticity in rod photoreceptors. Methods: We used Western blots and alkaline phosphatase (AP)-tagged neuropilin-1 (NPN-1) to detect the expression of Sema3A in an organotypic model of porcine retinal detachment. We then examined Sema3A binding to cultured salamander rod photoreceptors using AP-tagged Sema3A...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#6
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28796631/endocrine-disruption-in-human-fetal-testis-explants-by-individual-and-combined-exposures-to-selected-pharmaceuticals-pesticides-and-environmental-pollutants
#7
Pierre Gaudriault, Séverine Mazaud-Guittot, Vincent Lavoué, Isabelle Coiffec, Laurianne Lesné, Nathalie Dejucq-Rainsford, Martin Scholze, Andreas Kortenkamp, Bernard Jégou
BACKGROUND: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. OBJECTIVES: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals...
August 4, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28795301/organotypic-cultures-from-the-adult-cns-a-novel-model-to-study-demyelination-and-remyelination-ex-vivo
#8
Glaiza A Tan, Kendra L Furber, Merlin P Thangaraj, LaRhonda Sobchishin, J Ronald Doucette, Adil J Nazarali
Experimental models of multiple sclerosis (MS) have significantly advanced our understanding of pathophysiology and therapeutic interventions. Although in vivo rodent models are considered to most closely represent the complex cellular and molecular disease states of the human central nervous system (CNS), these can be costly to maintain and require long timelines. Organotypic slice cultures maintain the cytotypic organization observed in the intact CNS, yet provide many of the experimental advantages of in vitro cell culture models...
August 9, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28792475/human-papillomavirus-and-the-stroma-bidirectional-crosstalk-during-the-virus-life-cycle-and-carcinogenesis
#9
REVIEW
Megan E Spurgeon, Paul F Lambert
Human papillomaviruses (HPVs) are double-stranded DNA (dsDNA) tumor viruses that are causally associated with human cancers of the anogenital tract, skin, and oral cavity. Despite the availability of prophylactic vaccines, HPVs remain a major global health issue due to inadequate vaccine availability and vaccination coverage. The HPV life cycle is established and completed in the terminally differentiating stratified epithelia, and decades of research using in vitro organotypic raft cultures and in vivo genetically engineered mouse models have contributed to our understanding of the interactions between HPVs and the epithelium...
August 9, 2017: Viruses
https://www.readbyqxmd.com/read/28782169/impact-of-neonatal-hypoxia-ischaemia-on-oligodendrocyte-survival-maturation-and-myelinating-potential
#10
Malgorzata Ziemka-Nalecz, Justyna Janowska, Lukasz Strojek, Joanna Jaworska, Teresa Zalewska, Malgorzata Frontczak-Baniewicz, Joanna Sypecka
Hypoxic-ischaemic episodes experienced at the perinatal period commonly lead to a development of neurological disabilities and cognitive impairments in neonates or later in childhood. Clinical symptoms often are associated with the observed alterations in white matter in the brains of diseased children, suggesting contribution of triggered oligodendrocyte/myelin pathology to the resulting disorders. To date, the processes initiated by perinatal asphyxia remain unclear, hampering the ability to develop preventions...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28781061/dissecting-glioma-invasiveness-in-a-3d-organotypic-model
#11
Paolo Codega, Ingo K Mellinghoff
Diffuse brain infiltration by tumor cells is a hallmark of glioma. Molecular mechanisms of brain invasion are poorly understood due to the difficulty to model this process in culture. A new study published in Cell Reports developed a three-dimensional organotypic model and identified interferon regulatory factor 3 (IRF3) as repressor of glioma invasion.
August 3, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#12
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28771372/high-content-assay-multiplexing-for-vascular-toxicity-screening-in-induced-pluripotent-stem-cell-derived-endothelial-cells-and-human-umbilical-vein-endothelial-cells
#13
Yasuhiro Iwata, William D Klaren, Connie S Lebakken, Fabian A Grimm, Ivan Rusyn
Endothelial cells (ECs) play a major role in blood vessel formation and function. While there is longstanding evidence for the potential of chemical exposures to adversely affect EC function and vascular development, the hazard potential of chemicals with respect to vascular effects is not routinely evaluated in safety assessments. Induced pluripotent stem cell (iPSC)-derived ECs promise to provide a physiologically relevant, organotypic culture model that is amenable for high-throughput (HT) EC toxicant screening and may represent a viable alternative to traditional in vitro models, including human umbilical vein endothelial cells (HUVECs)...
August 3, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28763502/onset-of-microglial-entry-into-developing-quail-retina-coincides-with-increased-expression-of-active-caspase-3-and-is-mediated-by-extracellular-atp-and-udp
#14
María Martín-Estebané, Julio Navascués, Ana Sierra-Martín, Sandra M Martín-Guerrero, Miguel A Cuadros, María-Carmen Carrasco, José L Marín-Teva
Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina...
2017: PloS One
https://www.readbyqxmd.com/read/28763105/physiological-doses-of-red-light-induce-il-4-release-in-co-cultures-between-human-keratinocytes-and-immune-cells
#15
Cheryl Leong, Paul L Bigliardi, Gopu Sriram, Bijin Veonice Au, John Connolly, Mei Bigliardi-Qi
Phototherapy is routinely used for the treatment of various skin conditions and targeted therapy of superficial cancers. However, the molecular mechanisms behind their biological effects and the need for efficacy enhancing photosensitizers are not well addressed. Particularly, not much is known about the inherent effect of light from the visible spectrum on cytokine release and its downstream effects in keratinocytes and immune cells located in skin and therefore exposed to light. To address this, we delivered calibrated doses of well-defined light qualities (380 to 660 nm) to co-cultures of human keratinocytes and macrophage/dendritic cells in the absence or presence of the commonly used photosensitizer 8-methoxypsoralen (8-MOP)...
August 1, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28752668/comparison-of-two-decellularized-dermal-equivalents
#16
Shiuhyang Kuo, Hyungjin Myra Kim, Zhifa Wang, Eve L Bingham, Atsuko Miyazawa, Cynthia L Marcelo, Stephen E Feinberg
Immunologically inert allogeneic acellular dermal scaffolds provide a matrix with molecular architecture close to native tissues, which synthetic scaffolds cannot. Not all nature-derived scaffolds possess the same biological and physical properties. The different properties of scaffolds supporting cellular growth used for manufacturing tissue engineered grafts could lead to different implantation results. The scaffold properties should be carefully considered in order to meet the expected outcomes of tissue engineered grafts...
July 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28751459/pten-loss-increases-the-connectivity-of-fast-synaptic-motifs-and-functional-connectivity-in-a-developing-hippocampal-network
#17
Caitlynn M Barrows, Matthew P McCabe, Hongmei Chen, John W Swann, Matthew C Weston
Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN, causes epilepsy in humans and animal models, and altered mTOR signaling may contribute to a broad range of neurological diseases. Changes in synaptic transmission have been reported in animal models of PTEN loss; however, the full extent of these changes, and their effect on network function, is still unknown...
July 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28749338/fast-two-photon-imaging-of-subcellular-voltage-dynamics-in-neuronal-tissue-with-genetically-encoded-indicators
#18
Simon Chamberland, Helen H Yang, Michael M Pan, Stephen W Evans, Sihui Guan, Mariya Chavarha, Ying Yang, Charleen Salesse, Haodi Wu, Joseph C Wu, Thomas R Clandinin, Katalin Toth, Michael Z Lin, François St-Pierre
Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits, but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity...
July 27, 2017: ELife
https://www.readbyqxmd.com/read/28747710/a-high-content-image-analysis-approach-for-quantitative-measurements-of-chemosensitivity-in-patient-derived-tumor-microtissues
#19
Ilmari Ahonen, Malin Åkerfelt, Mervi Toriseva, Eva Oswald, Julia Schüler, Matthias Nees
Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746416/temporal-dynamics-of-ovine-airway-epithelial-cell-differentiation-at-an-air-liquid-interface
#20
Nicky O'Boyle, Erin Sutherland, Catherine C Berry, Robert L Davies
The respiratory tract and lungs are subject to diverse pathologies with wide-ranging implications for both human and animal welfare. The development and detailed characterization of cell culture models for studying such forms of disease is of critical importance. In recent years the use of air-liquid interface (ALI)-cultured airway epithelial cells has increased markedly, as this method of culture results in the formation of a highly representative, organotypic in vitro model system. In this study we have expanded on previous knowledge of differentiated ovine tracheal epithelial cells by analysing the progression of differentiation over an extensive time course at an ALI...
2017: PloS One
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