Accelerating the Development of Organs-on-Chips

Emulate, Inc. and AstraZeneca recently announced they have formed a collaborative partnership which will see Emulate's Organs-on-Chips technology embedded in AstraZeneca's Innovative Medicines and Early Development Biotech Unit.

To learn more about the partnership and what it hopes to achieve, as well as the benefits of using Organ-Chips, we spoke to Geraldine A. Hamilton, President and Chief Scientific Officer of Emulate, Inc., and Lorna Ewart, PhD, Head of Microphysiological Systems Centre of Excellence at AstraZeneca.

Anna MacDonald (AM): What are the main limitations of animal and cell models currently used in drug discovery and disease research?

Geraldine A. Hamilton (GH): The main limitations of today’s animal and cell models is that they do not fully represent the complexity of cells, tissues and organs in the human body.  These ‘gaps’ between conventional models and true human biology result in inefficiencies, safety issues, and lack of predictability in the drug development process.   

Lorna Ewart (LE): Organs-on-Chips technology allow us to gain the same or greater confidence that we currently get from animal models, so over time we may be able to reduce our reliance on these conventional models in drug development.

AM:  Can you tell us about the Human Emulation System and how it overcomes some of these limitations?

GH: Simply put, our Organ-Chips create a new living system that emulates human biology.  Emulate has designed our Human Emulation System to fully recreate the complex, dynamic state in which living cells function within a real human organ. This happens within Organ-Chips made from transparent polymers containing small fluidic channels that are lined with living human cells. Each Organ-Chip is approximately the size of a AA battery and houses tens of thousands of cells.

This unique approach to developing the Human Emulation System enables us to accurately recreate and modulate human biology and disease states.  In addition, the system contains three components – the Organ-Chips, instrumentation, and software apps – to create a lab-ready platform that can be used by any researcher, scientist, or product developer and fits within existing R&D workflows.  The end goal is for our system to enable human-relevant studies that can increase the success of drug discovery and development.   

AM: Emulate has recently partnered with AstraZeneca. How did this partnership arise, and what are the main aims?

GH: AstraZeneca began collaborating on this technology in 2013 – even before Emulate spun out as a start-up company from the Wyss Institute at Harvard University in July 2014.  This partnership is an example of how we can progress towards our goal of increasing the success of drug discovery and development by using our platform, which we call the Human Emulation System, to recreate human-relevant biology.

LE: Based on more than five years working with this technology, AstraZeneca is now looking at applying it across our therapy areas to study safety and efficacy of new drug candidates.  With this strategic agreement, AstraZeneca is the first pharmaceutical company to embed Emulate’s Organ-Chips technology into our own laboratories.  Our aims for the future are to improve R&D decision making by more accurately predicting the adverse and non-adverse effects of new drug candidates, as well as gain deeper insights into disease mechanisms – with the overall goal of accelerating drug discovery.

AM:  What are the next steps in the partnership after the initial focus of using the Liver-Chip to test drug safety? 

LE: Our initial focus on using the Liver-Chip for safety testing of drug candidates has already resulted in successful publication of recent work at a toxicology meeting in March 2018.  Beyond the Liver-Chip, AstraZeneca plans to advance deeper biological functionality of three other Organ-Chips to inform R&D decision making, with the aim of accelerating drug discovery and reducing reliance on animal models in the future.  The three additional Organ-Chips are:

• the Lung Tumor-Chip to explore the complex biology of lung tumors and the mechanisms contributing to drug resistance;

• the Lung-Chip to investigate mechanisms of chronic lung inflammation;

• the Glomerulus Kidney-Chip to study diabetes-induced kidney disease.

SEM image showing human ciliated cells inside Emulate’s Lung-Chip.

This collaboration allows for Emulate’s Organs-on-Chips technology to be adopted across AstraZeneca’s therapy areas, including cardiovascular and respiratory medicine, oncology, inflammation and autoimmune disease as well as drug safety and metabolism, to better predict safety and improve efficacy of new medicines.

AM: What are future applications using stem cells with Organs-on-Chips technology?

GH: Emulate is working with clinical partners at Cedars-Sinai Medical Center to produce Organ-Chips personalized with an individual patient’s stem cells, for applications in precision medicine.  This ‘Patient-on-a-Chip’ program opens up possibilities for a range of clinical applications that can benefit patients.  By placing a patient's cells in Organ-Chips and exposing those cells to a particular drug or series of drugs, clinicians could gain more accurate information about how that individual would respond to treatment, avoiding the risk of administering a drug that may cause harm or is ineffective and costly.  In the future, the Patient-on-a-Chip offers a new approach to precision medicine and personalized health, based on a patient’s genetic makeup and disease variants.

Geraldine Hamilton and Lorna Ewart were speaking to Anna MacDonald, Science Writer for Technology Networks.