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https://www.readbyqxmd.com/read/28548903/microenvironment-of-a-tumor-organoid-system-enhances-hepatocellular-carcinoma-malignancy-related-hallmarks
#1
Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu
Organ-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo...
May 26, 2017: Organogenesis
https://www.readbyqxmd.com/read/28546915/label-free-and-regenerative-electrochemical-microfluidic-biosensors-for-continual-monitoring-of-cell-secretomes
#2
Su Ryon Shin, Tugba Kilic, Yu Shrike Zhang, Huseyin Avci, Ning Hu, Duckjin Kim, Cristina Branco, Julio Aleman, Solange Massa, Antonia Silvestri, Jian Kang, Anna Desalvo, Mohammed Abdullah Hussaini, Su-Kyoung Chae, Alessandro Polini, Nupura Bhise, Mohammad Asif Hussain, HeaYeon Lee, Mehmet R Dokmeci, Ali Khademhosseini
Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label-free microfluidic electrochemical (EC) biosensor with a unique built-in on-chip regeneration capability for continual measurement of cell-secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported...
May 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28544655/3d-bioprinting-human-induced-pluripotent-stem-cell-constructs-for-in-situ-cell-proliferation-and-successive-multilineage-differentiation
#3
Qi Gu, Eva Tomaskovic-Crook, Gordon G Wallace, Jeremy M Crook
The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28543417/toward-public-bioethics
#4
EDITORIAL
Gregory E Kaebnick
This issue of the Hastings Center Report (May-June 2017) features a couple of interesting takes on the governance challenges of emerging technologies. In an essay on the National Academies of Science, Engineering, and Medicine report published this February on human germ-line gene editing, Eric Juengst, a philosopher at the University of North Carolina, argues that the NASEM committee did not manage to rethink the rules. Juengst reaches what he calls an "eccentric conclusion": "The committee's 2017 consensus report has been widely interpreted as 'opening the door' to inheritable human genetic modification and holding a line against enhancement interventions...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28534760/minibrain-storm-cerebral-organoids-aren-t-real-brains-but-they-provide-a-powerful-platform-for-modeling-brain-diseases-like-zika-infection-alzheimer-s-and-even-autism
#5
Shannon Fischer
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28534535/the-potential-of-organoids-in-urological-cancer-research
#6
REVIEW
Shangqian Wang, Dong Gao, Yu Chen
Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo...
May 23, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#7
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28520521/three-dimensional-cell-cultures-in-drug-discovery-and-development
#8
Ye Fang, Richard M Eglen
The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles...
June 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28516893/design-of-electrohydrodynamic-sprayed-polyethylene-glycol-hydrogel-microspheres-for-cell-encapsulation
#9
Anisa S Qayyum, Era Jain, Grant Kolar, Yonghyun Kim, Scott A Sell, Silviya P Zustiak
Electrohydrodynamic spraying (EHS) has recently gained popularity for microencapsulation of cells for applications in cell delivery and tissue engineering. Some of the polymers compatible with EHS are alginate, chitosan, and other similar natural polymers, which are subject to ionotropic or physical gelation. It is desirable to further extend the use of the EHS technique beyond such polymers for wider biofabrication applications. Here, building upon our previous work of making PEG microspheres via EHS, we utilized the principles of EHS to fabricate cell-laden polyethylene glycol (PEG) hydrogel microspheres...
May 18, 2017: Biofabrication
https://www.readbyqxmd.com/read/28512643/diagnostic-and-research-aspects-of-small-intestinal-disaccharidases-in-coeliac-disease
#10
REVIEW
Tanja Šuligoj, Paul J Ciclitira, Borut Božič
Disaccharidases (DS) are brush border enzymes embedded in the microvillous membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a general decrease of DS activities is seen. This manuscript reviews different aspects of DS activities in CD: their utility in the diagnosis and their application to in vitro toxicity testing. The latter has never been established in CD research. However, with the recent advances in small intestinal organoid techniques, DS might be employed as a biomarker for in vitro studies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28512141/oncogene-inducible-organoids-as-a-miniature-platform-to-assess-cancer-characteristics
#11
Tomohiro Mizutani, Yoshiyuki Tsukamoto, Hans Clevers
Direct effects of oncogenic proteins or inhibitor treatments on signaling pathways are difficult to assess in transgenic mice. In this issue, Riemer et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610058) demonstrate that oncogene-inducible organoids offer the experimental versatility of two-dimensional cell lines, while closely representing the in vivo situation.
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28510488/distinct-effects-of-growth-hormone-and-glutamine-on-activation-of-intestinal-stem-cells
#12
Yun Chen, Sheng-Hong Tseng, Chao-Ling Yao, Chuan Li, Ya-Hui Tsai
BACKGROUND: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining...
May 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28509388/proteomic-explorations-of-autism-spectrum-disorder
#13
Nicholas Szoko, Adam J McShane, Marvin R Natowicz
Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue...
May 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/28508073/three-dimensional-system-enabling-the-maintenance-and-directed-differentiation-of-pluripotent-stem-cells-under-defined-conditions
#14
Denise Zujur, Kosuke Kanke, Alexander C Lichtler, Hironori Hojo, Ung-Il Chung, Shinsuke Ohba
The development of in vitro models for the maintenance and differentiation of pluripotent stem cells (PSCs) is an active area of stem cell research. The strategies used so far are based mainly on two-dimensional (2D) cultures, in which cellular phenotypes are regulated by soluble factors. We show that a 3D culture system with atelocollagen porous scaffolds can significantly improve the outcome of the current platforms intended for the maintenance and lineage specification of mouse PSCs (mPSCs). Unlike 2D conditions, the 3D conditions maintained the undifferentiated state of mouse embryonic stem cells (mESCs) without exogenous stimulation and also supported endoderm, mesoderm, and ectoderm differentiation of mESCs under serum-free conditions...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28507600/insights-into-the-role-of-the-intestinal-microbiota-in-colon-cancer
#15
REVIEW
Sofia Oke, Alberto Martin
The intestinal microbiota consists of a dynamic organization of bacteria, viruses, archaea, and fungal species essential for maintaining gut homeostasis and protecting the host against pathogenic invasion. When dysregulated, the intestinal microbiota can contribute to colorectal cancer development. Though the microbiota is multifaceted in its ability to induce colorectal cancer, this review will focus on the capability of the microbiota to induce colorectal cancer through the modulation of immune function and the production of microbial-derived metabolites...
May 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28504681/fused-cerebral-organoids-model-interactions-between-brain-regions
#16
Joshua A Bagley, Daniel Reumann, Shan Bian, Julie Lévi-Strauss, Juergen A Knoblich
Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis...
May 10, 2017: Nature Methods
https://www.readbyqxmd.com/read/28504653/metabolic-shifts-in-residual-breast-cancer-drive-tumor-recurrence
#17
Kristina M Havas, Vladislava Milchevskaya, Ksenija Radic, Ashna Alladin, Eleni Kafkia, Marta Garcia, Jens Stolte, Bernd Klaus, Nicole Rotmensz, Toby J Gibson, Barbara Burwinkel, Andreas Schneeweiss, Giancarlo Pruneri, Kiran R Patil, Rocio Sotillo, Martin Jechlinger
Tumor recurrence is the leading cause of breast cancer-related death. Recurrences are largely driven by cancer cells that survive therapeutic intervention. This poorly understood population is referred to as minimal residual disease. Here, using mouse models that faithfully recapitulate human disease together with organoid cultures, we have demonstrated that residual cells acquire a transcriptionally distinct state from normal epithelium and primary tumors. Gene expression changes and functional characterization revealed altered lipid metabolism and elevated ROS as hallmarks of the cells that survive tumor regression...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28502841/use-of-airway-epithelial-cell-culture-to-unravel-the-pathogenesis-and-study-treatment-in-obstructive-airway-diseases
#18
REVIEW
Tinne C J Mertens, Harry Karmouty-Quintana, Christian Taube, Pieter S Hiemstra
Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct obstructive diseases. Both chronic diseases share a component of airway epithelial dysfunction. The airway epithelium is localized to deal with inhaled substances, and functions as a barrier preventing penetration of such substances into the body. In addition, the epithelium is involved in the regulation of both innate and adaptive immune responses following inhalation of particles, allergens and pathogens. Through triggering and inducing immune responses, airway epithelial cells contribute to the pathogenesis of both asthma and COPD...
May 11, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28501125/direct-orthotopic-implantation-of-hepatic-organoids
#19
Vivian X Zhou, Macarena Lolas, Tammy T Chang
BACKGROUND: Liver organoids show potential for development as a tissue replacement therapy for patients with end-stage liver disease, but efficient methods for introducing organoids into host livers have not been established. In this study, we aimed to develop a surgical technique to implant hepatic organoids into the liver and assess their engraftment. METHODS: Donor hepatocytes were isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into wild-type mice, could be easily identified by X-gal staining...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28500323/development-of-an-inducible-mouse-model-of-irfp713-to-track-recombinase-activity-and-tumour-development-in-vivo
#20
Andreas K Hock, Eric C Cheung, Timothy J Humpton, Tiziana Monteverde, Viola Paulus-Hock, Pearl Lee, Ewan McGhee, Alessandro Scopelliti, Daniel J Murphy, Douglas Strathdee, Karen Blyth, Karen H Vousden
While the use of bioluminescent proteins for molecular imaging is a powerful technology to further our understanding of complex processes, fluorescent labeling with visible light fluorescent proteins such as GFP and RFP suffers from poor tissue penetration and high background autofluorescence. To overcome these limitations, we generated an inducible knock-in mouse model of iRFP713. This model was used to assess Cre activity in a Rosa Cre-ER background and quantify Cre activity upon different tamoxifen treatments in several organs...
May 12, 2017: Scientific Reports
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