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https://www.readbyqxmd.com/read/28550311/organoid-based-epithelial-to-mesenchymal-transition-oemt-model-from-an-intestinal-fibrosis-perspective
#1
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
#2
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
#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/28534535/the-potential-of-organoids-in-urological-cancer-research
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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 five years 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
#11
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-organoids-culture-as-an-in-vitro-model-in-drug-metabolism-and-cytotoxicity-studies
#12
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 3D 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...
May 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28453760/long-term-inflammation-transforms-intestinal-epithelial-cells-of-colonic-organoids
#13
Shuji Hibiya, Kiichiro Tsuchiya, Ryohei Hayashi, Keita Fukushima, Nobukatsu Horita, Sho Watanabe, Tomoaki Shirasaki, Ryu Nishimura, Natsuko Kimura, Tatsunori Nishimura, Noriko Gotoh, Shigeru Oshima, Ryuichi Okamoto, Tetsuya Nakamura, Mamoru Watanabe
Background and Aims: Patients with ulcerative colitis [UC] are at an increased risk of developing colitis-associated cancer [CAC], suggesting that continuous inflammation in the colon promotes the transformation of colonic epithelial cells. However, the mechanisms underlying cell transformation in UC remain unknown. We therefore aimed to investigate the effect of long-term inflammation on intestinal epithelial cells [IECs] using organoid culture. Methods: IECs were isolated from mouse colon, and were cultured according to a method for a three-dimensional [3D] organoid culture...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28448600/mscs-feeder-layers-induce-smg-self-organization-and-branching-morphogenesis
#14
Mahmoud Farahat, Gulsan Ara Sathi, Emilio Satoshi Hara, Hiroaki Taketa, Takuo Kuboki, Takuya Matsumoto
Dysfunction of salivary glands leads to several oral health problems, including dental caries, mastication and swallowing dysfunctions and multiple oral infections. Conventional treatments for such condition fell short of providing satisfying therapeutic results. Recent advances in organ regeneration therapy which utilize tissue stem cells to fabricate bioengineered 3D organ buds, have introduced a promising therapeutic tool for full functional organ regeneration. However, finding a sustainable and easily accessible cell source for such approaches is still challenging, especially in case of severely atrophied tissues such as irradiated salivary glands...
2017: PloS One
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#15
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#16
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#17
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28416576/pathways-involved-in-formation-of-mammary-organoid-architecture-have-keys-to-understanding-drug-resistance-and-to-discovery-of-druggable-targets
#18
Saori Furuta, Mina J Bissell
Signals from the extracellular matrix (ECM) are received at the cell surface receptor, transmitted to the cytoskeletons, and transferred to the nucleus and chromatin for tissue- and context-specific gene expression. Cells, in return, modulate the cell shape and ECM, allowing for the maintenance of tissue homeostasis as well as for coevolution and adaptation to the environmental signals. We postulated the existence of dynamic and reciprocal interactions between the ECM and the nucleus more than three decades ago, but now these pathways have been proven experimentally thanks to the advances in imaging and cell/molecular biology techniques...
April 17, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28391362/stem-cell-derived-organoids-and-their-application-for-medical-research-and-patient-treatment
#19
REVIEW
Sina Bartfeld, Hans Clevers
3D culture has allowed the initiation and expansion of organ-like structures, called organoids, from either tissue-resident adult stem cells or pluripotent stem cells. Today, organoids can be grown to resemble a wide variety of organs, exhibiting remarkable similarity to their in vivo counterparts. As successful organoid generation is possible from virtually every patient, organoids hold a great promise for medical research and the development of new treatments. They have already found their way into the clinic, enabling personalized medicine in small patient trials...
April 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28373686/an-update-on-stem-cell-biology-and-engineering-for-brain-development
#20
C J C Parr, S Yamanaka, H Saito
Two recent technologies, induced-pluripotent stem cells (iPSCs) and direct somatic reprogramming, have shown enormous potential for cell-based therapies against intractable diseases such as those that affect the central nervous system. Already, methods that generate most major cell types of the human brain exist. Whether the cell types are directly reprogrammed from human somatic cells or differentiated from an iPSC intermediate, the overview presented here demonstrates how these protocols vary greatly in their efficiencies, purity and maturation of the resulting cells...
June 2017: Molecular Psychiatry
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