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https://www.readbyqxmd.com/read/29773424/a-device-for-high-throughput-monitoring-of-degradation-in-soft-tissue-samples
#1
D S Tzeranis, I Panagiotopoulos, S Gkouma, G Kanakaris, N Georgiou, N Vaindirlis, G Vasileiou, M Neidlin, A Gkousioudi, V Spitas, G A Macheras, L G Alexopoulos
This work describes the design and validation of a novel device, the High-Throughput Degradation Monitoring Device (HDD), for monitoring the degradation of 24 soft tissue samples over incubation periods of several days inside a cell culture incubator. The device quantifies sample degradation by monitoring its deformation induced by a static gravity load. Initial instrument design and experimental protocol development focused on quantifying cartilage degeneration. Characterization of measurement errors, caused mainly by thermal transients and by translating the instrument sensor, demonstrated that HDD can quantify sample degradation with <6 μm precision and <10 μm temperature-induced errors...
May 3, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29769543/the-cytokine-secretion-profile-of-mesenchymal-stromal-cells-is-determined-by-surface-structure-of-the-microenvironment
#2
Daniëlle G Leuning, Nick R M Beijer, Nadia A du Fossé, Steven Vermeulen, Ellen Lievers, Cees van Kooten, Ton J Rabelink, Jan de Boer
Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29766664/tissue-engineered-nigrostriatal-pathway-for-treatment-of-parkinson-s-disease
#3
Laura A Struzyna, Kevin D Browne, Zachary D Brodnik, Justin C Burrell, James P Harris, H Isaac Chen, John A Wolf, Kate V Panzer, James Lim, John E Duda, Rodrigo A España, D Kacy Cullen
The classic motor deficits of Parkinson's disease are caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of their long-distance axonal projections that modulate the striatum. Current treatments only minimize the symptoms of this disconnection as there is no approach capable of replacing the nigrostriatal pathway. We are applying micro-tissue engineering techniques to create living, implantable constructs that mimic the architecture and function of the nigrostriatal pathway...
May 15, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29766029/seizure-suppressant-and-neuroprotective-effects-of-encapsulated-bdnf-producing-cells-in-a-rat-model-of-temporal-lobe-epilepsy
#4
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29763736/generating-a-recombinant-phosphothreonine-binding-domain-for-a-phosphopeptide-of-the-human-transcription-factor-c-myc
#5
Leon A Venegas, Stefanie L Kall, Oluwadamilola Bankole, Arnon Lavie, Brian Kay
Transcription factor c-Myc is an oncoprotein that is regulated at the post-translational level through phosphorylation of two conserved residues, Serine 62 (Ser62) and Threonine 58 (Thr58). A highly specific tool capable of recognizing Myc via pThr58 is needed to monitor activation and localization. Through phage display, we have isolated 10 engineered Forkhead-associated (FHA) domains that selectively bind to a phosphothreonine (pThr)-containing peptide (53-FELLPpTPPLSPS-64) segment of human c-Myc. One domain variant was observed to bind to the Myc-pThr58 peptide with a KD value of 800 nM and had >1,000-fold discrimination between the phosphorylated and non-phosphorylated peptide...
May 12, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29761549/sprifermin-treatment-enhances-cartilage-integration-in-an-in-vitro-repair-model
#6
Mackenzie L Sennett, Gregory R Meloni, Alexandra J E Farran, Hans Guehring, Robert L Mauck, George R Dodge
Cartilage integration remains a clinical challenge for treatment of focal articular defects. Cartilage exhibits limited healing capacity that declines with tissue maturation. Many approaches have been investigated for their ability to stimulate healing of mature cartilage or integration of repair tissue or tissue-engineered constructs with native cartilage. Growth factors present in immature tissue may enhance chondrogenesis and promote integrative repair of cartilage defects. In this study, we assessed the role of one such factor, fibroblast growth factor 18 (FGF18)...
May 14, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29760942/induction-of-chondrogenesis-of-human-placenta-derived-mesenchymal-stem-cells-via-heparin-grafted-human-fibroblast-derived-matrix
#7
Yong Kwan Noh, Ping Du, Avelino Dos Santos Da Costa, Kwideok Park
Background: Formation of mature and functional articular cartilage is still challenging in cartilage tissue engineering. This study investigates the potential of using heparin-grafted decellularized extracellular matrix (ECM) as a novel growth factor delivery platform towards human placenta-derived mesenchymal stem cells (hPMSCs) chondrogenic differentiation. Human fibroblast-derived extracellular matrix (hFDM) is naturally obtained from in vitro-cultured human lung fibroblasts via a mild decellularization process...
2018: Biomaterials Research
https://www.readbyqxmd.com/read/29757956/osteogenic-differentiation-modulates-the-cytokine-chemokine-and-growth-factor-profile-of-ascs-and-shed
#8
Federico Mussano, Tullio Genova, Sara Petrillo, Ilaria Roato, Riccardo Ferracini, Luca Munaron
Great efforts have been made to improve bone regeneration techniques owing to a growing variety of sources of stem cells suitable for autologous transplants. Specifically, adipose-derived stem cells (ASCs) and stems cells from human exfoliated deciduous teeth (SHED) hold great potential for bone tissue engineering and cell therapy. After a preliminary characterization of the main biomolecules ASCs and SHED released in their conditioned media, cells were kept both in normal and osteo-inducing conditions. Conventional assays were performed to prove their osteogenic potential such as quantitative real-time polymerase chain reaction (qRT-PCR) (for RUNX-2, collagen type I, osteopontin and osteonectin), alkaline phosphatase activity, osteocalcin production, and von Kossa staining...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29757143/tumor-derived-csf-1-induces-the-nkg2d-ligand-rae-1%C3%AE-on-tumor-infiltrating-macrophages
#9
Thornton W Thompson, Benjamin T Jackson, P Jonathan Li, Jiaxi Wang, Alexander Byungsuk Kim, Kristen Ting Hui Huang, Lily Zhang, David H Raulet
NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo ...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29756600/the-development-of-neural-stimulators-a-review-of-preclinical-safety-and-efficacy-studies
#10
Robert K Shepherd, Joel Villalobos, Owen Burns, David Nayagam
OBJECTIVE: Given the rapid expansion of the field of neural stimulation and the rigorous regulatory approval requirements required before these devices can be applied clinically, it is important that there is clarity around conducting preclinical safety and efficacy studies required for the development of this technology. APPROACH: The present review examines basic design principles associated with the development of a safe neural stimulator and describes the suite of preclinical safety studies that need to be considered when taking a device to clinical trial...
May 14, 2018: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29756533/genetic-engineering-of-mesenchymal-stem-cells-for-differential-matrix-deposition-on-3dwoven-scaffold
#11
Nguyen Phuong Thao Huynh, Jonathan Matthew Brunger, Catherine Claire Gloss, Franklin T Moutos, Charles A Gersbach, Farshid Guilak
Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to the inherent complexities of inducing cartilage-like matrix and bone-like matrix within the same local environment. Members of the transforming growth factor β (TGFβ) family have been extensively utilized in the engineering of skeletal tissues, but have distinct effects on chondrogenic and osteogenic differentiation of progenitor cells. The goal of this study was to develop a method to direct human bone marrow derived mesenchymal stem cells (MSCs) to deposit either mineralized matrix or a cartilaginous matrix rich in glycosaminoglycan and type II collagen within the same biochemical environment...
May 14, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29756272/harnessing-human-decellularized-blood-vessel-matrices-and-cellular-construct-implants-to-promote-bone-healing-in-an-ex-vivo-organotypic-bone-defect-model
#12
Stefanie Inglis, Karl Heinrich Schneider, Janos M Kanczler, Heinz Redl, Richard O C Oreffo
Decellularized matrices offer a beneficial substitute for biomimetic scaffolds in tissue engineering. The current study examines the potential of decellularized placental vessel sleeves (PVS) as a periosteal protective sleeve to enhance bone regeneration in embryonic day 18 chick femurs contained within the PVS and cultured organotypically over a 10 day period. The femurs are inserted into decellularized biocompatibility-tested PVS and maintained in an organotypic culture for a period of 10 days. In femurs containing decellularized PVS, a significant increase in bone volume (p < 0...
May 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29754201/skin-bioprinting-a-novel-approach-for-creating-artificial-skin-from-synthetic-and-natural-building-blocks
#13
Robin Augustine
Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue...
May 12, 2018: Progress in Biomaterials
https://www.readbyqxmd.com/read/29752426/protein-engineering-on-human-recombinant-follistatin-enhancing-pharmacokinetic-characteristics-for-therapeutic-application
#14
Chuan Shen, Andrea Iskenderian, Dianna Lundberg, Tao He, Kathleen Palmieri, Robert Crooker, Qingwei Deng, Matthew Traylor, Sheng Gu, Haojing Rong, David Ehmann, Brian Pescatore, Bettina Strack-Logue, Alla Romashko, George Baviello, John Gill, Bohong Zhang, Muthuraman Meiyappan, Clark Pan, Angela W Norton
Follistatin (FS) is an important regulatory protein, a natural antagonist for transforming growth factor beta family members activin and myostatin. The diverse biological roles of the activin and myostatin signaling pathways make FS a promising therapeutic target for treating human diseases exhibiting inflammation, fibrosis and muscle disorders, such as Duchenne muscular dystrophy. However, rapid heparin-mediated hepatic clearance of FS limits its therapeutic potential. We targeted the heparin binding loop of FS for site-directed mutagenesis to improve clearance parameters...
May 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29752081/effect-of-polyhydroxybutyrate-chitosan-bioglass-nanofiber-scaffold-on-proliferation-and-differentiation-of-stem-cells-from-human-exfoliated-deciduous-teeth-into-odontoblast-like-cells
#15
Maryam Khoroushi, Mohammad Reza Foroughi, Saeed Karbasi, Batool Hashemibeni, Abbas Ali Khademi
Scaffolds and their characteristics play a central role in tissue engineering. The purpose of this study was to determine the effects of Polyhydroxybutyrate (PHB)/Chitosan/nano-bioglass (nBG) nanofiber scaffold made using the electrospinning method, on the proliferation and differentiation of stem cells obtained from human exfoliated deciduous teeth into odontoblast-like cells. In this experimental study, the pulps of the molten deciduous teeth were isolated, thereafter, the stem cells from human exfoliated deciduous teeth (SHED) were extracted and then the 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell viability percentage...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29751776/negative-effects-of-a-high-tumour-necrosis-factor-%C3%AE-concentration-on-human-gingival-mesenchymal-stem-cell-trophism-the-use-of-natural-compounds-as-modulatory-agents
#16
Chiara Giacomelli, Letizia Natali, Marco Nisi, Marinella De Leo, Simona Daniele, Barbara Costa, Filippo Graziani, Mario Gabriele, Alessandra Braca, M Letizia Trincavelli, Claudia Martini
BACKGROUND: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29751775/cxcl12-engineered-endothelial-progenitor-cells-enhance-neurogenesis-and-angiogenesis-after-ischemic-brain-injury-in-mice
#17
Yaning Li, Shuang Chang, Wanlu Li, Guanghui Tang, Yuanyuan Ma, Yanqun Liu, Fang Yuan, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang
BACKGROUND: Ischemic stroke causes a multitude of brain damage. Neurovascular injury and myelin sheath degradation are two manifestations of ischemic brain damage. Therapeutic strategies aiming only at repairing the neural components or the vessels cannot efficiently restore neurological function. Endothelial progenitor cells (EPCs) have the advantages of both promoting angiogenesis and secreting trophic factors that would promote neurogenesis. Chemokine cxcl12 gene therapy has also been shown to promote angiogenesis, neurogenesis, and remyelination, attracting EPCs, neural progenitor cells, and oligodendrocyte progenitor cells (OPCs) to the injured sites of the brain...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29750840/advances-on-a-decision-analytic-approach-to-exposure-based-chemical-prioritization
#18
Matthew D Wood, Kenton Plourde, Sabrina Larkin, Peter P Egeghy, Antony J Williams, Valerie Zemba, Igor Linkov, Daniel A Vallero
The volume and variety of manufactured chemicals is increasing, although little is known about the risks associated with the frequency and extent of human exposure to most chemicals. The EPA and the recent signing of the Lautenberg Act have both signaled the need for high-throughput methods to characterize and screen chemicals based on exposure potential, such that more comprehensive toxicity research can be informed. Prior work of Mitchell et al. using multicriteria decision analysis tools to prioritize chemicals for further research is enhanced here, resulting in a high-level chemical prioritization tool for risk-based screening...
May 11, 2018: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/29748524/high-affinity-promotes-internalization-of-engineered-antibodies-targeting-fgfr1
#19
Łukasz Opaliński, Jakub Szymczyk, Martyna Szczepara, Marika Kucińska, Daniel Krowarsch, Małgorzata Zakrzewska, Jacek Otlewski
Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) fused to highly cytotoxic drugs (warheads)...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29748209/tas6417-a-novel-epidermal-growth-factor-receptor-inhibitor-targeting-exon-20-insertion-mutations
#20
Shinichi Hasako, Miki Terasaka, Naomi Abe, Takao Uno, Hirokazu Ohsawa, Akihiro Hashimoto, Ryoto Fujita, Kenji Tanaka, Takashige Okayama, Renu Wadhwa, Kazutaka Miyadera, Yoshimi Aoyagi, Kazuhiko Yonekura, Kenichi Matsuo
Activating mutations in the epidermal growth factor receptor (EGFR) gene are important targets in cancer therapy because they are key drivers of non-small-cell lung cancer (NSCLC). Whereas almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy...
May 10, 2018: Molecular Cancer Therapeutics
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