Cell Cultures in Drug Discovery: An Industrial Perspective

Author(s):  
Anna‐Lena Ungell ◽  
Johan Karlsson
Keyword(s):  
2020 ◽  
Vol 21 (18) ◽  
pp. 6806 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Michele Sommariva ◽  
Nicoletta Gagliano ◽  
...  

In the last decade, three-dimensional (3D) cell culture technology has gained a lot of interest due to its ability to better recapitulate the in vivo organization and microenvironment of in vitro cultured cancer cells. In particular, 3D tumor models have demonstrated several different characteristics compared with traditional two-dimensional (2D) cultures and have provided an interesting link between the latter and animal experiments. Indeed, 3D cell cultures represent a useful platform for the identification of the biological features of cancer cells as well as for the screening of novel antitumor agents. The present review is aimed at summarizing the most common 3D cell culture methods and applications, with a focus on prostate cancer modeling and drug discovery.


2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Sigrid A Langhans ◽  
Peter Worthington ◽  
Kathleen Drake ◽  
Zhiqin Li ◽  
Andrew Napper ◽  
...  

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i36-i36
Author(s):  
Yannick Berker ◽  
Dina ElHarouni ◽  
Heike Peterziel ◽  
Ina Oehme ◽  
Matthias Schlesner ◽  
...  

Abstract Introduction Image-based phenotypic drug profiling is receiving increasing attention in drug discovery and precision medicine. Compared to classical end-point measurements quantifying drug response, image-based profiling enables both the quantification of drug response and characterization of disease entities and drug mechanisms of actions. In pediatric precision oncology, we aim to study drug response in patient-derived 3D spheroid tumor cell cultures and tackle the challenges of a lack of image-segmentation methods and limited patient-derived material. Methods We investigate deep transfer learning with patient-by-patient fine-tuning for cell-viability quantification. We fine-tune a convolutional neural network (pre-trained on ImageNet) with many cell-line-specific and few patient-specific assay controls. The method is validated using 3D cell cultures in 384-well microplates derived from cell lines with known drug sensitivities and tested with primary patient-derived samples. Network outputs at different drug concentrations are used for drug-sensitivity scoring; dense-layer activations are used in t-distributed stochastic neighbor embedding and clustering of drugs. Results Cell-line experiments confirm expected hits, such as effective treatment with BRAF inhibitors in a BRAF V600E mutated brain tumor model and NTRK inhibitors in a cell line harboring an NTRK-fusion, indicating the predictive power of deep learning to identify drug-hit candidates for individual patients. In patient-derived samples, clustering of drugs further confirms phenotypic similarity according to their mechanisms of actions. Combining drug scoring with phenotypic clustering may provide opportunities for complementary combination treatments. Conclusion Deep transfer learning with patient-by-patient fine-tuning is a promising, segmentation-free image-analysis approach for precision medicine and drug discovery based on 3D spheroid cell cultures.


2017 ◽  
Vol 22 (5) ◽  
pp. 456-472 ◽  
Author(s):  
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.


2017 ◽  
Vol 37 (5) ◽  
pp. 2201-2210 ◽  
Author(s):  
JAN HAGEMANN ◽  
CHRISTIAN JACOBI ◽  
MORITZ HAHN ◽  
VANESSA SCHMID ◽  
CHRISTIAN WELZ ◽  
...  

Author(s):  
Gunter F. Thomas ◽  
M. David Hoggan

In 1968, Sugimura and Yanagawa described a small 25 nm virus like particle in association with the Matsuda strain of infectious canine hepatitis virus (ICHV). Domoto and Yanagawa showed that this particle was dependent on ICHV for its replication in primary dog kidney cell cultures (PDK) and was resistant to heating at 70°C for 10 min, and concluded that it was a canine adeno-associated virus (CAAV). Later studies by Onuma and Yanagawa compared CAAV with the known human serotypes (AAV 1, 2, 3) and AAV-4, known to be associated with African Green Monkeys. Using the complement fixation (CF) test, they found that CAAV was serologically related to AAV-3 and had wide distribution in the dog population of Japan.


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