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Cell Culture


THREE-DIMENSIONAL ORGANOID CELL CULTURE optimising disease models for research and drug discovery


The use of human-induced pluripotent stem cells (HiPSCs) continues to grow in three-dimensional (3D) spheroid and organoid culture. Although advances in 3D cell culture systems are improving drug target validation and lead optimisation, it is the advancement of organoid cell culture that is making a significant impact in disease modelling and drug discovery.


I


n this article, we examine the use of organoid cell culture systems as applied to cancer research and the development of novel anti-


oncologic drugs. Collectively, this transition from 3D spheroid culture to organoid culture allows researchers to generate multiple organ-specific cell types, resulting in cell architectures that more closely resemble the human tissue microenviron- ment. Furthermore, researchers are generating organoid cultures that are increasingly complex and more phenotypically relevant and, as a result, optimal models are being established to better understand patient-specific tumour proliferation and invasion patterns.


Increasingly-complex 3D models As 3D cell culture has become more widely accept- ed, researchers have become more proficient with 3D techniques and the models being created have


Drug Discovery World Spring 2019


become more complex. Researchers now create spheroids made of multiple cells types1, combine tools to create advanced co-culture models2 and are recapitulating organs from stem cells, including human iPS (HiPSCs) cells to the form of organoids3. These recent advances in 3D cell culture and


greater adoption of HiPSCs for basic research and drug discovery are coalescing to generate systems that provide numerous advantages over more tra- ditional, established culturing systems. While 3D systems provide more in vivo-like tissue environ- ments in which to study cell function, patient- derived HiPSCs provide a better model of human disease pathophysiology than other model systems. Consequently, researchers can now better study the complex in vivo functionality of tissue and organ systems, and can monitor patient-specific response to treatment prior to clinical evaluation4. As dis- cussed in a prior issue of this publication,


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By Dr Amanda Linkous, Hilary Sherman, Iris Li and Dr Richard M. Eglen


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