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Ludger Schöls
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October 17, 2016: JAMA Neurology
David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, Justin A Kinsella, Günes Altiokka Uzun, Merih Karbay, Zeynep Tüfekçioglu, Hasmet Hanagasi, Georgina Burke, Nicola Foulds, Simon R Hammans, Anupam Bhattacharjee, Heather Wilson, Matthew Adams, Mark Walker, James A R Nicoll, Jeremy Chataway, Nick Fox, Indran Davagnanam, Rahul Phadke, Henry Houlden
Importance: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations...
October 17, 2016: JAMA Neurology
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Maria Sanchez-Mico, Raquel Sanchez-Varo, Cristina Nuñez-Diaz, Laura Trujillo-Estrada, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica
The role of microglial cells in the development and progression of Alzheimer's disease (AD) has not been elucidated. Here, we demonstrated the existence of a weak microglial response in human AD hippocampus which is in contrast to the massive microglial activation observed in APP-based models. Most importantly, microglial cells displayed a prominent degenerative profile (dentate gyrus > CA3 > CA1 > parahippocampal gyrus), including fragmented and dystrophic processes with spheroids, a reduced numerical density, and a significant decrease in the area of surveillance ("microglial domain")...
October 14, 2016: Acta Neuropathologica
Eric Lauga, Sébastien Michelin
Active particles disturb the fluid around them as force dipoles, or stresslets, which govern their collective dynamics. Unlike swimming speeds, the stresslets of active particles are rarely determined due to the lack of a suitable theoretical framework for arbitrary geometry. We propose a general method, based on the reciprocal theorem of Stokes flows, to compute stresslets as integrals of the velocities on the particle's surface, which we illustrate for spheroidal chemically active particles. Our method will allow tuning the stresslet of artificial swimmers and tailoring their collective motion in complex environments...
September 30, 2016: Physical Review Letters
Jian Deng, Lubao Teng, C P Caulfield, Xuerui Mao
We propose a natural model to probe in a controlled fashion the instability of interacting vortex rings shed from the edge of an oblate spheroid disk of major diameter c, undergoing oscillations of frequency f_{0} and amplitude A. We perform a Floquet stability analysis to determine the characteristics of the instability modes, which depend strongly on the azimuthal (integer) wave number m. We vary two key control parameters, the Keulegan-Carpenter number K_{C}=2πA/c and the Stokes number β=f_{0}c^{2}/ν, where ν is the kinematic viscosity of the fluid...
September 2016: Physical Review. E
Fatemeh Mahmoodi, Hassan Akrami
Placental growth factor (PlGF) a member of the vascular endothelial growth factor family regulates some cell processes such as survival, growth of vascular endothelial cells, invasiveness and also involves in pathological angiogenesis and metastasis in most cancers. Cancer stem cells are believed to be the main reason for the tumor relapse and resistance to therapy. These cells have various characteristics as same as normal tissue-specific adult stem cells, including self-renewability and potent to differentiate into various cell types...
October 13, 2016: Journal of Cellular Biochemistry
Marta Cavo, Marco Fato, Leonardo Peñuela, Francesco Beltrame, Roberto Raiteri, Silvia Scaglione
Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and in pathological conditions. In particular, mechanical and chemical stimuli play a relevant role on cell fate, cancer onset and malignant evolution. Here, we use mechanically-tuned alginate hydrogels to study the role of substrate elasticity on breast adenocarcinoma cell activity. The hydrogel elastic modulus (E) was measured via atomic force microscopy (AFM) and a remarkable range (150-4000 kPa) was obtained...
October 13, 2016: Scientific Reports
S Dini, B J Binder, S C Fischer, C Mattheyer, A Schmitz, E H K Stelzer, N G Bean, J E F Green
Automatic identification of the necrotic zone boundary is important in the assessment of treatments on in vitro tumour spheroids. This has been difficult especially when the difference in cell density between the necrotic and viable zones of a tumour spheroid is small. To help overcome this problem, we developed novel one-dimensional pair-correlation functions (PCFs) to provide quantitative estimates of the radial distance of the necrotic zone boundary from the centre of a tumour spheroid. We validate our approach on synthetic tumour spheroids in which the position of the necrotic zone boundary is known a priori It is then applied to nine real tumour spheroids imaged with light sheet-based fluorescence microscopy...
October 2016: Journal of the Royal Society, Interface
Liliana R Cisneros Castillo, Andrei-Dumitru Oancea, Christian Stüllein, Anne Régnier-Vigouroux
Multicellular tumor spheroids (MCTSs) embedded in a matrix are re-emerging as a powerful alternative to monolayer-based cultures. The primary information gained from a three-dimensional model is the invasiveness of treatment-exposed MCTSs through the acquisition of light microscopy images. The amount and complexity of the acquired data and the bias arisen by their manual analysis are disadvantages calling for an automated, high-throughput analysis. We present a universal algorithm we developed with the scope of being robust enough to handle images of various qualities and various invasion profiles...
October 12, 2016: Scientific Reports
Chiara Giverso, Pasquale Ciarletta
Multicellular tumour spheroids (MCTSs) are extensively used as in vitro system models for investigating the avascular growth phase of solid tumours. In this work, we propose a continuous growth model of heterogeneous MCTSs within a porous material, taking into account a diffusing nutrient from the surrounding material directing both the proliferation rate and the mobility of tumour cells. At the time scale of interest, the MCTS behaves as an incompressible viscous fluid expanding inside a porous medium. The cell motion and proliferation rate are modelled using a non-convective chemotactic mass flux, driving the cell expansion in the direction of the external nutrients' source...
October 2016: European Physical Journal. E, Soft Matter
Honghai Xia, Jun Cao, Qing Li, Yang Lv, Weidong Jia, Weihua Ren, Qingyu Cheng, Xiaoyuan Song, Geliang Xu
The recent identification of "Side Population" (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 10(2) cells/mouse). The mRNA microarray analysis of the SP vs...
October 11, 2016: Scientific Reports
F G Mitri
The analysis using the partial-wave series expansion (PWSE) method in spherical coordinates is extended to evaluate the acoustic radiation force experienced by rigid oblate and prolate spheroids centered on the axis of wave propagation of high-order Bessel vortex beams composed of progressive, standing and quasi-standing waves, respectively. A coupled system of linear equations is derived after applying the Neumann boundary condition for an immovable surface in a non-viscous fluid, and solved numerically by matrix inversion after performing a single numerical integration procedure...
September 30, 2016: Ultrasonics
Mingzhu Yin, Xia Li, Shu Tan, Huanjiao Jenny Zhou, Weidong Ji, Stefania Bellone, Xiaocao Xu, Haifeng Zhang, Alessandro D Santin, Ge Lou, Wang Min
Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage-like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM...
October 10, 2016: Journal of Clinical Investigation
Michael J Susienka, Benjamin T Wilks, Jeffrey R Morgan
Tissue fusion, whereby two or more spheroids coalesce, is a process that is fundamental to biofabrication. We have designed a quantitative, high-throughput platform to investigate the fusion of multicellular spheroids using agarose micro-molds. Spheroids of primary human chondrocytes (HCH) or human breast cancer cells (MCF-7) were self-assembled for 24 h and then brought together to form an array comprised of two spheroids (one doublet) per well. To quantify spheroid fusogenicity, we developed two assays: (1) an initial tack assay, defined as the minimum amount of time for two spheroids to form a mechanically stable tissue complex or doublet, and (2) a fusion assay, in which we defined and tracked key morphological parameters of the doublets as a function of time using wide-field fluorescence microscopy over a 24 h time-lapse...
October 10, 2016: Biofabrication
B Q Wei, N Yan, J X Gao, D D Li, Z G Shang, K He
This paper studies the absolute thickness measurement of pyrolytic graphite spheroids (GSs) by using STEM-EELS mode with log-ratio method and Kramers-Kroning (K-K) method, taking the measured thickness from TEM image as reference that is the diameter of GSs ranging from 60 to 250nm. The effect of collection semi-angle (β) on thickness measurement has been investigated. It is found that in general the thickness obtained by K-K analysis with surface effect corrected shows the best accuracy, followed by K-K sum rule and then log-ratio method for the three different collection semi-angles of 12...
October 4, 2016: Micron: the International Research and Review Journal for Microscopy
Virginia Brancato, Alessandro Garziano, Filomena Gioiella, Francesco Urciuolo, Giorgia Imparato, Valeria Panzetta, Sabato Fusco, Paolo A Netti
: We fabricated three-dimensional microtissues with the aim to replicate in vitro the composition and the functionalities of the tumor microenvironment. By arranging either normal fibroblasts (NF) or cancer-activated fibroblasts (CAF) in two different three dimensional (3D) configurations, two kinds of micromodules were produced: spheroids and microtissues. Spheroids were obtained by means of the traditional cell aggregation technique resulting in a 3D model characterized by high cell density and low amount of extracellular proteins...
October 6, 2016: Acta Biomaterialia
Wenli Zhang, Caibin Li, Bruce C Baguley, Fang Zhou, Weisai Zhou, John P Shaw, Zhen Wang, Zimei Wu, Jianping Liu
To obtain a multicellular MCF-7 spheroid model to mimic the three-dimensional (3D) of tumors, the microwell liquid overlay (A) and hanging-drop/agar (B) methods were first compared for their technical parameters. Then a method for embedding spheroids within collagen was optimized. For method A, centrifugation assisted cells form irregular aggregates but not spheroids. For method B, an extended sedimentation period of over 24 h for cell suspensions and increased viscosity of the culture medium using methylcellulose were necessary to harvest a dense and regular cell spheroid...
October 5, 2016: Analytical Biochemistry
Lauren E Jamieson, Victoria L Camus, Pierre O Bagnaninchi, Kate M Fisher, Grant D Stewart, William H Nailon, Duncan B McLaren, David J Harrison, Colin J Campbell
Use of multicellular tumor spheroids (MTS) to investigate therapies has gained impetus because they have potential to mimic factors including zonation, hypoxia and drug-resistance. However, analysis remains difficult and often destroys 3D integrity. Here we report an optical technique using targeted nanosensors that allows in situ 3D mapping of redox potential gradients whilst retaining MTS morphology and function. The magnitude of the redox potential gradient can be quantified as a free energy difference (ΔG) and used as a measurement of MTS viability...
September 22, 2016: Nanoscale
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