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Cell Culture


References 1 Lazzari, Gianpiero et al. Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity. Acta biomaterialia 78 (2018): 296-307. 2 Sherman, Hilary, Gitschier, Hannah J and Rossi, Ann Elizabeth. A Novel Three- Dimensional Immune Oncology Model for High- Throughput Testing of Tumoricidal Activity. Frontiers in immunology 9 (2018): 857. 3 Fatehullah, Aliya, Tan, Si Hui and Barker, Nick. Organoids as an in vitro model of human development and disease. Nature cell biology 18.3 (2016): 246. 4 Fang, Y, Eglen, RM. Three- Dimensional Cell Cultures in Drug Discovery and Development. SLAS Discovery. 2017, 22, 456-472. 5 Chen, H. Isaac, Song, Hongjun and Ming, Guo li. Applications of human brain organoids to clinical problems. Developmental Dynamics 248.1 (2019): 53-64. 6 Hallam, Dean et al. Human Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient Dependent Efficiency. Stem Cells 36.10 (2018): 1535-1551. 7 McCracken, Kyle W et al. Generating human intestinal tissue from pluripotent stem cells in vitro. Nature protocols6.12 (2011): 1920. 8 Nie, Yun-Zhong et al. Human liver organoids generated with single donor-derived multiple cells rescue mice from acute liver failure. Stem cell research & therapy 9.1 (2018): 5. 9 Dye, Briana R et al. In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4 (2015): e05098. 10 Hoang, Plansky et al. Generation of spatial- patterned early-developing cardiac organoids using human pluripotent stem cells. Nature protocols 13.4 (2018): 723.


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Figure 1: Intestinal organoids


organoids – and more complex organ systems – are now being leveraged for lead optimisation, includ- ing estimations of compound preclinical toxicity and potential metabolic liability. Using HiPSCs, several organoids have now been


generated including brain5, eye6, intestine7 (Figure 1), liver8, lung9, heart10 and kidney11 (summarised in Table 1). These models offer researchers a tool to better study tissue formation, renewal and func- tion while maintaining many of the disease charac- teristics of the individual from which the cells were sourced3.


CELL TYPE AND DESCRIPTION


Brain Cortical culture microfluidic arrays


Disease modelling – AD, cortex Cortical layering


Midbrain cultures


Eye Retinal optic cup


Heart Cardiac modelling


Gut Gut-ENS co-cultures


Table 1:Human organoid cell types Drug Discovery World Spring 2019


3D cell culture and cancer research Cancer researchers were among the first to adopt 3D cell culture systems, principally as development of 3D cell culture systems facilitates study of host-tumour interactions. In addition, progress has been made in the use of 3D cell systems in high throughput screen- ing for cancer drug discovery and development. A diverse array of model systems is available to


investigate the disease mechanisms that promote tumorigenesis. Such systems range from simplistic 2D cultures that rarely recapitulate the true com- plexity of human cancer, to very expensive and


FUNCTION


Ca2+ ion imaging, electrical activity Neurite outgrowth and viability A, phosphorylated tau protein Astrocytes, glutamate/GABA neurons Circuit activity, Ca2+ imaging Patch-clamp electrophysiology Express TH+ DA neurons, electrophysiology


Functional photoreceptors and RPEs Electrophysiology


Ca2+ ion imaging, muscle contraction Video imaging of beating


Ca2+ ion imaging, muscle contraction REFERENCES 20, 26-31


31 26, 27 26


32 33-35, 36-40 41, 42


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