Cookies

Like most websites The Translational Scientist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Research Field Drug discovery, Animal models, Biomedical engineering

A Model Experiment

With just one in 10 preclinical candidates in phase I trials likely to gain market approval, the pharmaceutical industry must find ways to develop effective therapeutics faster and more cost-effectively. Pipelines include a mix of drug discovery, redevelopment, repurposing, combination therapeutics, and new modalities, such as gene therapies or regenerative medicines. When it comes to success, however, the translatability of preclinical data into clinical efficacy is only as good as the predictivity of the test models…

Drug discovery traditionally involves two-dimensional monolayer cell culture experiments followed by testing in animals to ensure results translate in vivo. Unfortunately, these models suffer from well-documented inefficiencies and inaccuracies, including oversimplification, insufficient representation of the underlying pathophysiology, and interspecies differences – all of which can lead to poor translatability into the clinic.

Microphysiological systems (MPS) are a relatively new approach that combines bioengineering and cell biology to provide more physiologically relevant data in early R&D stages. MPS build on the concepts of traditional two-dimensional assays, but improve physiological relevance by mimicking aspects of organ function. Systems such as 3D spheroids, organoids, organ-on-a-chip, multi-organs on chips, static micropatterned technologies, and physiome-on-a-chip models combine living cells and microfluidic technologies with drug delivery, stimulation, or sensing tools to gain a clearer picture of how such tools will function in a living organism. The technology’s broad applications extend into modelling healthy or diseased organs, studying multi-organ interactions, investigating ADME and toxicity, and screening, identifying, and ranking drug candidates. Single- and multi-organ MPS technologies are designed to mimic specific aspects of organ function or crosstalk; for instance, an MPS that incorporates liver tissue with another organ offers the opportunity to concurrently study efficacy and susceptibility to toxicity. For highly prevalent diseases with well-established impacts on public health, they can also enable investigations into host genetics, treatment responses, novel therapeutic targets, and additional biomarkers. Such investigations are increasingly important for conditions such as non-alcoholic steatohepatitis (NASH), for which there are currently no therapies on the market. Microtissue models of human NASH demonstrate key hallmarks of the disease, giving researchers the opportunity to mimic the stages of disease and elucidate its pathophysiological mechanisms on a cellular level.

By improving risk predictivity over standard research tools, or by providing a more comprehensive model that is not otherwise available, MPS could bridge the gap between traditional cell culture and human studies. But, to maximize their potential, insights gathered from these models should be considered alongside in vivo data – both to provide confidence in the data derived from MPS models and to offer insight into the mechanisms underlying differences and adverse events in animal models. Ultimately, single- and multi-organ MPS could yield efficiency gains, reduce costs, and potentially reduce animal usage.

As MPS technology continues to evolve, advances in the field are extending the lifespan of models, enabling a greater window for long-term experiments, compound dosing, and observations of disease progression – and edging us ever closer to a true simulation of human biological conditions.

Enjoy our FREE content!

Log in or register to gain full unlimited access to all content on the The Translational Scientist site. It’s FREE!

Login

Or register now - it’s free!

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts

When you click “Register” we will email you a link, which you must click to verify the email address above and activate your account. If you do not receive this email, please contact us at [email protected].

About the Author

Audrey Dubourg

Product Manager at CN Bio Innovations Ltd., Cambridge, UK.

Register to The Translational Scientist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts

Register