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3D organoid

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https://www.readbyqxmd.com/read/28314175/choosing-wisely-preclinical-test-models-in-the-era-of-precision-medicine
#1
REVIEW
Konrad Klinghammer, Wolfgang Walther, Jens Hoffmann
Through the introduction of a steadily growing variety of preclinical test models drug development and biomarker research has advanced. Next to classical used 2D cell line cultures, tissue-slice cultures, 3D organoid cell cultures, genetically engineered mouse models, cell line derived mouse models and patient derived xenografts may be selected for a specific question. All models harbor advantages and disadvantages. This review focuses on the available preclinical test models, novel developments such as humanized mice and discusses for which question a particular model should be employed...
March 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28314117/three-dimensional-cell-cultures-in-drug-discovery-and-development
#2
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...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28303935/multiscale-microenvironmental-perturbation-of-pluripotent-stem-cell-fate-and-self-organization
#3
Yoji Tabata, Matthias P Lutolf
The combination of microfluidics with engineered three-dimensional (3D) matrices can bring new insights into the fate regulation of stem cells and their self-organization into organoids. Although there has been progress in 3D stem cell culturing, most existing in vitro methodologies do not allow for mimicking of the spatiotemporal heterogeneity of stimuli that drive morphogenetic processes in vivo. To address this, we present a perfusion-free microchip concept for the in vitro 3D perturbation of stem cell fate...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292842/bringing-together-the-organoid-field-from-early-beginnings-to-the-road-ahead
#4
REVIEW
Senthil K Muthuswamy
From October 12-15th, 2016, EMBO∣EMBL held a symposium to bring together those in the scientific community with a shared interest in using three-dimensional (3D) culture methods to study biology, model disease and personalize treatments. The symposium, entitled 'Organoids: modelling organ development and disease in 3D culture', which was organized by Juergen Knoblich, Mina Bissell and Esther Schnapp, was particularly timely as there were otherwise few opportunities for those interested in using 3D culture platforms to interact outside of their organ-specific scientific community...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28287550/forskolin-induced-swelling-in-intestinal-organoids-an-in-vitro-assay-for-assessing-drug-response-in-cystic-fibrosis-patients
#5
Sylvia F Boj, Annelotte M Vonk, Marvin Statia, Jinyi Su, Robert R G Vries, Jeffrey M Beekman, Hans Clevers
Recently-developed cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs correct surface expression and/or function of the mutant CFTR channel in subjects with cystic fibrosis (CF). Identification of subjects that may benefit from these drugs is challenging because of the extensive heterogeneity of CFTR mutations, as well as other unknown factors that contribute to individual drug efficacy. Here, we describe a simple and relatively rapid assay for measuring individual CFTR function and response to CFTR modulators in vitro...
February 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28283582/self-organized-developmental-patterning-and-differentiation-in-cerebral-organoids
#6
Magdalena Renner, Madeline A Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A Knoblich
Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28277923/3d-culture-as-a-clinically-relevant-model-for-personalized-medicine
#7
Eliza Li Shan Fong, Tan Boon Toh, Hanry Yu, Edward Kai-Hua Chow
Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient...
March 1, 2017: SLAS Technol
https://www.readbyqxmd.com/read/28265064/multisensor-integrated-organs-on-chips-platform-for-automated-and-continual-in-situ-monitoring-of-organoid-behaviors
#8
Yu Shrike Zhang, Julio Aleman, Su Ryon Shin, Tugba Kilic, Duckjin Kim, Seyed Ali Mousavi Shaegh, Solange Massa, Reza Riahi, Sukyoung Chae, Ning Hu, Huseyin Avci, Weijia Zhang, Antonia Silvestri, Amir Sanati Nezhad, Ahmad Manbohi, Fabio De Ferrari, Alessandro Polini, Giovanni Calzone, Noor Shaikh, Parissa Alerasool, Erica Budina, Jian Kang, Nupura Bhise, João Ribas, Adel Pourmand, Aleksander Skardal, Thomas Shupe, Colin E Bishop, Mehmet Remzi Dokmeci, Anthony Atala, Ali Khademhosseini
Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28257659/comprehensive-assessment-of-cucurbitacin-e-related-hepatotoxicity-and-drug-drug-interactions-involving-cyp3a-and-p-glycoprotein
#9
Jian Lu, Yuanjin Zhang, Min Sun, Mingyao Liu, Xin Wang
BACKGROUND: Cucurbitacin E (CuE), a tetracyclic triterpenoid isolated from Cucurbitaceae, possesses many pharmacological activities especially anti-cancer. PURPOSE: The aim of this investigation was to comprehensively assess CuE related hepatotoxicity and potential drug-drug interactions involving CYP3A and P-glycoprotein (P-gp). STUDY DESIGN AND METHODS: Four common cytotoxicity assays (MTS, SRB, NRU and apoptosis assays) were used to evaluate the hepatotoxicity of CuE in human hepatocellular carcinoma HepG2 cells...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28251176/bioprinting-the-cancer-microenvironment
#10
Yu Shrike Zhang, Margaux Duchamp, Rahmi Oklu, Leif W Ellisen, Robert Langer, Ali Khademhosseini
Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies...
October 10, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28242812/crispr-knockout-of-the-hur-gene-causes-a-xenograft-lethal-phenotype
#11
Shruti Lal, Edwin C Cheung, Mahsa Zarei, Ranjan Preet, Saswati N Chand, Nicole C Mambelli-Lisboa, Carmella Romeo, Matthew C Stout, Eric Londin, Austin Goetz, Cinthya Y Lowder, Avinoam Nevler, Charles J Yeo, Paul M Campbell, Jordan M Winter, Dan A Dixon, Jonathan R Brody
Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer related deaths in the U.S., while colorectal cancer (CRC) is the third most common cancer. The RNA binding protein HuR (ELAVL1), supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and CRC tumor cohorts as compared to normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and CRC (HCT116) cell lines...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28220493/dawn-of-the-organoid-era-3d-tissue-and-organ-cultures-revolutionize-the-study-of-development-disease-and-regeneration
#12
Ninouk Akkerman, Libert H K Defize
Novel and updated approaches of culturing cells in 3D are rapidly advancing our understanding of development, health, and disease. As tissues have been found to behave more realistically in 3D than in 2D cultures, organoid technology in combination with recent advances in the isolation and generation of stem cells, has rapidly become a promising concept in developmental and regenerative research. The development of all kinds of tissues can now be studied "in a dish," allowing more detailed observations of stem cell maintenance, morphogens, and differentiation...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28211365/converging-biofabrication-and-organoid-technologies-the-next-frontier-in-hepatic-and-intestinal-tissue-engineering
#13
Kerstin Schneeberger, Bart Spee, Pedro Costa, Norman Sachs, Hans Clevers, Jos Malda
Adult tissue stem cells can form self-organizing 3D organoids in vitro. Organoids resemble small units of their organ of origin and have great potential for tissue engineering, as well as models of disease. However, current culture technology limits the size, architecture and complexity of organoids. Here, we review the establishment of intestinal and hepatic organoids and discuss how the convergence of organoids and biofabrication technologies can help overcome current limitations, and thereby further advance the translational application of organoids in tissue engineering and regenerative medicine...
March 6, 2017: Biofabrication
https://www.readbyqxmd.com/read/28202491/organoid-technologies-meet-genome-engineering
#14
REVIEW
Jing Nie, Eri Hashino
Three-dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two-dimensional (2D) cell culture models. Organoids, the 3D self-organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28188103/kidney-organoids-a-translational-journey
#15
REVIEW
Ryuji Morizane, Joseph V Bonventre
Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing...
March 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28174092/pancreatic-cancer-models-for-translational-research
#16
REVIEW
Diana Behrens, Wolfgang Walther, Iduna Fichtner
No abstract text is available yet for this article.
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28167491/simplified-3d-protocol-capable-of-generating-early-cortical-neuroepithelium
#17
Dwayne B Holmes, Vivi M Heine
Here, we report a 3D cerebellar differentiation protocol with quick startup method, defined medium and no special materials or handling requirements. Three fibroblast growth factors (FGF2, 4 and 8) were used for cerebellar patterning and smoothened agonist (SAG) for granule cell development. After 35 days, differentiation products exhibited similar structures and neuronal markers reported in prior 'organoid' and 'spheroid' protocols. This included cells positive for KIRREL2 (a marker of early cerebellar neuroepithelium) and ZIC1 (a marker for granule cells)...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28159716/cellular-self-assembly-and-biomaterials-based-organoid-models-of-development-and-diseases
#18
REVIEW
Shivem B Shah, Ankur Singh
Organogenesis and morphogenesis have informed our understanding of physiology, pathophysiology, and avenues to create new curative and regenerative therapies. Thus far, this understanding has been hindered by the lack of a physiologically relevant yet accessible model that affords biological control. Recently, three-dimensional ex vivo cellular cultures created through cellular self-assembly under natural extracellular matrix cues or through biomaterial-based directed assembly have been shown to physically resemble and recapture some functionality of target organs...
January 31, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28143999/3d-hydrogel-based-microwell-arrays-as-a-tumor-microenvironment-model-to-study-breast-cancer-growth
#19
John Casey, Xiaoshan Yue, Trung Dung Nguyen, Aylin Acun, Victoria R Zellmer, Siyuan Zhang, Pinar Zorlutuna
The tumor microenvironment (TME) is distinctly heterogeneous and is involved in tumor growth, metastasis, and drug resistance. Mimicking this diverse microenvironment is essential for understanding tumor growth and metastasis. Despite the substantial scientific progress made with traditional cell culture methods, microfabricated three-dimensional (3D) cell cultures that can be precisely controlled to mimic the changes occur in the TME over tumor progression are necessary for simulating organ-specific TME in vitro...
March 15, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28135257/one-step-generation-of-conditional-and-reversible-gene-knockouts
#20
Amanda Andersson-Rolf, Roxana C Mustata, Alessandra Merenda, Jihoon Kim, Sajith Perera, Tiago Grego, Katie Andrews, Katie Tremble, José C R Silva, Juergen Fink, William C Skarnes, Bon-Kyoung Koo
Loss-of-function studies are key for investigating gene function, and CRISPR technology has made genome editing widely accessible in model organisms and cells. However, conditional gene inactivation in diploid cells is still difficult to achieve. Here, we present CRISPR-FLIP, a strategy that provides an efficient, rapid and scalable method for biallelic conditional gene knockouts in diploid or aneuploid cells, such as pluripotent stem cells, 3D organoids and cell lines, by co-delivery of CRISPR-Cas9 and a universal conditional intronic cassette...
March 2017: Nature Methods
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