Cell Culture
translate to substantial savings in drug discovery and development.
Rules of composition for higher order systems Modularity and the integration of functional parts into higher order systems is not only a fundamental ingredient for industrial success, it is also a basic design principle of biology. Our body is made of organs which are made up by tissues, which in turn are made up by cells. With the advent of 3D tissue models, we moved from cells to tissues. To get clos- er to the human patient, it can be necessary to go beyond tissues and explore organs and connected organ systems. Microphysiological Systems (MPS) or Body-on-a-Chip (BOC) systems provide plat- forms to connect tissue models in fluidic channels. Until recently, bioengineering of 3D tissues focused on cellular composition and structure. In higher order systems, the environment in which the tissues are cultured, becomes much more important. It has been widely recognised that physiological flow influencing mass transport and shear forces, as well as physio-mechanical cues, can have a critical impact on tissue function and drug-tissue interac- tion. Beyond the local tissue environment, organ function is decisively determined by interactions with other organs in the human body through endocrine signalling. Engineering multi-organ sys- tems expands the challenges of model development to include micro-engineering, microfluidics and logistics. Microfluidic systems can substantially increase experimental complexity not only by a more sophisticated set-up including tubing, pumps and microfluidic labware, but also through the requirement of intricate set-up protocols. A com- plete and reliable organ system can be generated only if it can be ensured that every element of the system (ie every single organ model as well as every technical part) functions properly and produces trustworthy results. Furthermore, modularity, sim- plicity and the introduction of QC steps on the bio- logical and technical level are key for establishing multi-tissue experiments with high reproducibility and acceptable throughput. As described above, the production and matura-
tion of organ models after in vivo extraction needs to follow stringent protocols to preserve maximal viability and organ-specific functions. Protocols may vary in time and in most cases are incompati- ble with each other requiring isolated production and subsequent assembly. This poses challenges in timing, logistics and on-site, gentle multi-organ assembly and operation, for which we are develop- ing novel, modular and robust solutions.
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Despite these hurdles, higher organ systems open
new doors in pre-clinical testing. While in the past, studying and modelling organ-organ interaction was only available in animal models or human tri- als, MPS enables transfer of systemic insights to the pre-clinical in vitro stage. More interesting is that, in contrast to animals, organ-organ interaction can be systematically built-up or dissected to elucidate on-target or off-target effects.
Conclusions Recent technological and scientific developments now make it possible to build human in vitro 3D tissue models and even connected 3D tissue/organ models recapitulating human biology and patho- physiologies with a rapidly-increasing faithfulness. While it is a continuous work in progress to improve these systems and make them even more reliable, the potential in risk reduction, increase in predictivity, time savings and cost savings are so significant that hardly any company in the drug discovery and development field can ignore these developments. It is only a matter of time before we can truly engineer in vitro disease models that truly bring the bench closer to the bedside. When that happens, no one will want to be left behind.DDW
Dr Patrick Guye is Chief Scientific Officer at InSphero AG. Patrick has extensive experience in life sciences and bioengineering and has held lead- ership positions in both industry and academia. His research interests include cell therapy, 3D cel- lular models/organoids, synthetic biology, human stem cells, biologics/small molecules development and precision genomic engineering.
Dr Eva Thoma is Head of Liver Solutions at InSphero AG. A biomedical scientist with exten- sive experience in cell biology and the development of advanced cell models for drug discovery and development, Eva has held research management positions in pharmaceutical and biotech industries. Her team develops highly-sophisticated, inducible liver disease models.
Dr Olivier Frey is Head of Technology and Platforms at InSphero AG. Olivier is a bioengi- neering and microfluidics expert with a passion for microphysiological systems. His team is responsi- ble for delivering the scalable 3D plate and flow technology that enables researchers to interrogate and interconnect advanced 3D models in organ- on-a-chip networks.
Drug Discovery World Winter 2018/19
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