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https://www.readbyqxmd.com/read/28644395/optical-tracking-and-digital-quantification-of-beating-behavior-in-bioengineered-human-cardiac-organoids
#1
Mahesh Devarasetty, Steven Forsythe, Thomas D Shupe, Shay Soker, Colin E Bishop, Anthony Atala, Aleksander Skardal
Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging...
June 23, 2017: Biosensors
https://www.readbyqxmd.com/read/28643936/phenotypic-analysis-of-organoids-by-proteomics
#2
REVIEW
Alexis Gonneaud, Claude Asselin, François Boudreau, François-Michel Boisvert
The development of 3D cell cultures into self-organizing organ-like structures named organoids provides a model that better reflects in vivo organ physiology and their functional properties. Organoids have been established from several organs, such as the intestine, prostate, brain, liver, kidney and pancreas. With recent advances in high-throughput and -omics profiling technologies, it is now possible to study the mechanisms of cellular organisation at the systems level. It is therefore not surprising that these methods are now used to characterize organoids at the transcriptomic, proteomic, chromatin state and transcription factor DNA-binding levels...
June 23, 2017: Proteomics
https://www.readbyqxmd.com/read/28640507/a-liver-specific-gene-expression-panel-predicts-the-differentiation-status-of-in-vitro-hepatocyte-models
#3
Dae-Soo Kim, Jea-Woon Ryu, Mi-Young Son, Jung-Hwa Oh, Kyung-Sook Chung, Sugi Lee, Jeong-Ju Lee, Jun-Ho Ahn, Ju-Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho-Rok Jung, Nam-Soon Kim, Hyun-Soo Cho
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies...
June 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28615312/stem-cells-in-repair-of-gastrointestinal-epithelia
#4
REVIEW
Amanda Andersson-Rolf, Matthias Zilbauer, Bon-Kyoung Koo, Hans Clevers
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity...
July 2017: Physiology
https://www.readbyqxmd.com/read/28599598/uniform-neural-tissue-models-produced-on-synthetic-hydrogels-using-standard-culture-techniques
#5
Christopher Barry, Matthew T Schmitz, Nicholas E Propson, Zhonggang Hou, Jue Zhang, Bao K Nguyen, Jennifer M Bolin, Peng Jiang, Brian E McIntosh, Mitchell D Probasco, Scott Swanson, Ron Stewart, James A Thomson, Michael P Schwartz, William L Murphy
The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28589925/mesenchymal-stem-cells-support-growth-and-organization-of-host-liver-colorectal-tumor-organoids-and-possibly-resistance-to-chemotherapy
#6
Mahesh Devarasetty, Edina Wang, Shay Soker, Aleksander Skardal
Despite having yielded extensive breakthroughs in cancer research, traditional 2D cell cultures have limitations in studying cancer progression and metastasis and screening therapeutic candidates. 3D systems can allow cells to grow, migrate, and interact with each other and the surrounding matrix, resulting in more realistic constructs. Furthermore, interactions between host tissue and developing tumors influence the susceptibility of tumors to drug treatments. Host-liver colorectal-tumor spheroids composed of primary human hepatocytes, mesenchymal stem cells (MSC) and colon carcinoma HCT116 cells were created in simulated microgravity rotating wall vessel (RWV) bioreactors...
June 7, 2017: Biofabrication
https://www.readbyqxmd.com/read/28562594/guided-self-organization-and-cortical-plate-formation-in-human-brain-organoids
#7
Madeline A Lancaster, Nina S Corsini, Simone Wolfinger, E Hilary Gustafson, Alex W Phillips, Thomas R Burkard, Tomoki Otani, Frederick J Livesey, Juergen A Knoblich
Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies...
May 31, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28559141/establishment-of-a-refined-culture-method-for-rat-colon-organoids
#8
Hiroyuki Isshiki, Yoshiaki Arimura, Kanna Nagaishi, Kentaro Kawakami, Kei Onodera, Kentaro Yamashita, Yasuyoshi Naishiro, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura
BACKGROUND: Methods for the artificial three-dimensional (3D) culture of mouse and human small-intestinal and large-intestinal stem cells have been established with CD24(+) or Paneth cell niches. In contrast, no studies have established stable 3D culture for rat colon stem cells. In this study, we established an advanced method for efficient rat colonic stem cell culture. METHODS: Using various tissue homogenates, we investigated the colonic organoid forming capacity under the TMDU protocol immediately adjacent to Ootani's 3D culture assembly in the same culture dish...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28550311/organoid-based-epithelial-to-mesenchymal-transition-oemt-model-from-an-intestinal-fibrosis-perspective
#9
Soojung Hahn, Myeong-Ok Nam, Jung Hyun Noh, Dong Hyeon Lee, Hyun Wook Han, Duk Hwan Kim, Ki Baik Hahm, Sung Pyo Hong, Jun-Hwan Yoo, Jongman Yoo
The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28548903/microenvironment-of-a-tumor-organoid-system-enhances-hepatocellular-carcinoma-malignancy-related-hallmarks
#10
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/28544655/3d-bioprinting-human-induced-pluripotent-stem-cell-constructs-for-in-situ-cell-proliferation-and-successive-multilineage-differentiation
#11
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/28534535/the-potential-of-organoids-in-urological-cancer-research
#12
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/28520521/three-dimensional-cell-cultures-in-drug-discovery-and-development
#13
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/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/28504681/fused-cerebral-organoids-model-interactions-between-brain-regions
#15
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/28500323/development-of-an-inducible-mouse-model-of-irfp713-to-track-recombinase-activity-and-tumour-development-in-vivo
#16
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
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#17
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
May 10, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28475412/pi3k-akt-mtor-axis-sustains-rotavirus-infection-via-the-4e-bp1-mediated-autophagy-pathway-and-represents-an-antiviral-target
#18
Yuebang Yin, Wen Dang, Xinying Zhou, Lei Xu, Wenshi Wang, Wanlu Cao, Sunrui Chen, Junhong Su, Xuepeng Cai, Shaobo Xiao, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies...
May 5, 2017: Virulence
https://www.readbyqxmd.com/read/28468988/adam12-induction-by-twist1-promotes-tumor-invasion-and-metastasis-via-regulation-of-invadopodia-and-focal-adhesions
#19
Mark A Eckert, Miguel Santiago-Medina, Thinzar M Lwin, Jihoon Kim, Sara A Courtneidge, Jing Yang
The Twist1 transcription factor promotes tumor invasion and metastasis by inducing Epithelial-Mesenchymal Transition (EMT) and invadopodia-mediated extracellular matrix degradation. The critical transcription targets of Twist1 in mediating these events remain to be uncovered. Here, we report that Twist1 strongly induces expression of a disintegrin and metalloprotease 12 (ADAM12). Expression levels of Twist1 and ADAM12 are tightly correlated in human breast tumors. Knocking down ADAM12 blocked cell invasion in the 3D mammary organoid culture...
May 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28468837/crypt-organoid-culture-as-an-in-vitro-model-in-drug-metabolism-and-cytotoxicity-studies
#20
Wenqi Lu, Eva Rettenmeier, Miles Paszek, Mei-Fei Yueh, Robert H Tukey, Jocelyn Trottier, Olivier Barbier, Shujuan Chen
The gastrointestinal tract is enriched with xenobiotic processing proteins that play important roles in xenobiotic bioactivation, metabolism, and detoxification. The application of genetically modified mouse models has been instrumental in characterizing the function of xenobiotic processing genes (XPG) and their proteins in drug metabolism. Here, we report the utilization of three-dimensional crypt organoid cultures from these animal models to study intestinal drug metabolism and toxicity. With the successful culturing of crypt organoids, we profiled the abundance of Phase I and Phase II XPG expression, drug transporter gene expression, and xenobiotic nuclear receptor (XNR) gene expression...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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