Drug Discovery
3D organoid cell culture
3D Organoid Cell Culture - Optimising disease models for research and drug discovery

3D Organoid Cell Culture - Optimising disease models for research and drug discovery

By Dr Amanda Linkous, Hilary Sherman, Iris Li and Dr Richard M. Eglen
Spring 2019

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.

In this article, we examine the use of organoid cell culture systems as applied to cancer research and the development of novel antioncologic 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 microenvironment. 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 accepted, researchers have become more proficient with 3D techniques and the models being created have become more complex. Researchers now create spheroids made of multiple cells types (1), combine tools to create advanced co-culture models (2) and are recapitulating organs from stem cells, including human iPS (HiPSCs) cells to the form of organoids (3).

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 traditional, established culturing systems. While 3D systems provide more in vivo-like tissue environments in which to study cell function, patientderived 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 evaluation (4). As discussed in a prior issue of this publication, organoids – and more complex organ systems – are now being leveraged for lead optimisation, including estimations of compound preclinical toxicity and potential metabolic liability.

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