Making organs in miniature01/09/17Health
Cherry Biotech’s Pierre Gaudriault, R&D project manager, shares his thoughts on the future of organs-on-chips, their potential as alternatives to animal testing, and the challenges in developing a realistic human-on-a-chip.
Organs-on-chips consist of a flexible and translucent microfluidic chip which is roughly the size of a USB flash drive and lined with living human cells arranged in such a way as to replicate tissue and organ physiology. The result is a small in vitro device that not only mimics the real-life function of an organ but also simulates its response to drugs or disease.
The excitement behind organs-on-chips can be easily explained by the limitations of the current drug development process: animal studies can take years to complete, testing even a single compound is becoming increasingly expensive, very few new drugs are actually reaching patients, cells cultured in dishes often die or don’t work as normal outside the body, and trial/test results seen in animals don’t necessarily translate to humans.
The use of organ-on-a-chip technology in place of traditional animal and cell culture models therefore has the potential to revolutionise drug development, making trials shorter, cheaper, more accurate and, of course, far more animal friendly. What’s more, organs-on-chips open the door to truly personalised medicine – medicines tailored to a patient’s specific disease or tested on their own cells.
Championing the growth of organ-on-a-chip technology in Europe is Cherry Biotech SAS, a France-based company that works to develop scientific instruments for use in cell biology research laboratories. Speaking to Pan European Networks, R&D project manager Pierre Gaudriault provides his thoughts on the future of organs-on-chips, their potential as alternatives to animal testing, and the work going on at Cherry Biotech towards the first functional human-on-a-chip platform.
How does Cherry Biotech envision the future of organ-on-a-chip technologies?
Organs-on-chips have applications in multiple fields. Among them is obviously drug development, cosmetics tests, as well as chemical safety testing and (rare) disease modelling. Furthermore, due to their fidelity to physiology they might be used in fundamental research to better explain organ function.
At Cherry Biotech we believe that organ-on-a-chip technologies will be the next generation of in vitro assays. Our vision is really that organs-on-chips will fill the gaps between what is currently being observed in early stage drug development and chemical safety assays, and what is being observed in the actual human population. Up until now we have had only a few tools that can be used in early stage in vitro assays, and those tools aren’t wholly predictable or necessarily efficient enough to assess the effect of something in humans. We assume therefore that organs-on-chips will bridge the gap between in vitro and reality.
How might organ-on-a-chip models overcome the limitations of animal testing and cell culture models?
One of the most used animal models is mice, particularly during the drug development stages and in chemical safety testing. While we have no doubt that mouse models provide very useful information, we still have some gaps between the results obtained in these animals and the reality witnessed in humans – because, for example, some of the biological pathways in a human might not be affected by a certain chemical in the same way that they are in an animal, or certain organs might be organised differently. Essentially, organ-on-a-chip technologies more closely replicate human (patho)physiology and so might be a good alternative to animal testing.
How far does the regulatory model around drug development in Europe support the use of organ-on-a-chip technology?
The principles of the 3Rs (Replace, Reduce, Refine) are already in place. Put simply, the 3Rs are aimed at ensuring animal testing is humane by avoiding or replacing the use of ‘protected’ animals, reducing the number of animals used in an experiment, and taking care to minimise the pain and suffering that an animal might experience as a result of an experiment. We believe that this regulatory framework is the first step towards the use of organ-on-a-chip technology as opposed to animal testing.
However, we don’t yet have any idea of what exact regulations might be needed to approve organ-on-a-chip technology or what they might look like. Maybe it will be the case that specific regulations are needed for each individual application. At the moment, we just don’t know, and we will need to be patient because, of course, regulators need to think and take into consideration all the possibilities and outcomes of such a new model.
How far can a human-on-a-chip model realistically reproduce the complexities of the human body, and what are some of the main hurdles to achieving this goal?
This is a very interesting question and it’s something we are very keen to explore at Cherry Biotech. First, we need to be absolutely sure that each organ-on-a-chip is the real image of the human organ from a physiological point of view. Next, we need to find a way to interconnect each of these different organs, and that interconnection is perhaps one of the biggest challenges that industry and science will have to address in the next ten years. It might be that you simply connect the organs using plastic tubes, but plastic tubes aren’t the same thing as blood vessels, and while growing blood vessels is becoming more and more easy, growing blood vessels between different organs is still a huge challenge.
How best to feed the organs is another challenge. What medium do you use? Will an external pump be enough to provide sufficient oxygen and nutrients? Or is something else required?
We will also need to think about the medium composition. The mediums that are classically used in cell culture are typically designed to promote cell proliferation, but with organs-on-chips cell proliferation is not the real end point; you just need to keep your organs alive and functional. Because different organs have different needs and require different conditions, scientists and SMEs will need to find medium compositions that manage to both keep each different organ alive and at the same time maintain an environment that is sufficient – in terms of nutrient delivery, for instance – to preserve the functionality of each organ.
These are the key challenges we need to address when thinking about the human-on-a-chip.
How is Cherry Biotech working to advance organ-on-a-chip technology in Europe?
What we ultimately want to do is understand the needs and biology of each individual organ so that we can push forwards the different applications of organ-on-a-chip technology.
To give an example, one of our projects is SeCtOR ENABleRs (Standard Collagenous ORgans-on-chip ENvisaging Advanced Biological Researches), which is funded by Horizon 2020 and aims to develop a user-friendly, multipurpose and tailored platform to allow the scientific community to be able to replicate the complexity of tissue and organs – essentially, it will create an organ-on-a-chip ‘starter pack’ that can then be used to unleash the full power of microfluidics.
We’re also being supported by Bpifrance’s i-LAB scheme to deliver a human-on-a-chip research programme. Through the development of interconnected organs-on-chips, we want to develop the first human-on-a-chip for preclinical and clinical assays, and we are inviting highly skilled young scientists to help us achieve this ambitious goal by joining our Entrepreneurship Unit.
Cherry Biotech believes that partnership and collaboration are far and away the best way to promote organ-on-a-chip technologies, particularly in the scientific field. The European Commission is similarly very keen to promote partnerships between SMEs and academic or research organisations, and this is reflected in its funding programmes. As such, all of our organ-on-a-chip-related European projects contain links between us and academia, and we are open to all kinds of collaboration, regardless of the chosen organ.
About the author
I am Pierre Gaudriault, currently working at Cherry Biotech (Rennes, France) as R&D project manager. I obtained a PharmD in 2013 and then a PhD in 2016.
At the beginning of my scholarship, I wanted to enrol in the army. I clearly remember the day when everything changed: it was in a biology class, where for the very first time I looked at onion skin cells under a microscope. Suddenly the army was no longer an option. After this revelation, I designed my education route to better understand biology, with a particular focus on how the human body works. I then became passionate about how some chemicals might affect organs and human health, and so have been introduced into toxicology.
During my pharmaceutical study, I had this crazy idea to connect multiple mini-organs to better assess the chemical safety and prevent public health issues. I figured out a few years later that this idea wasn’t so crazy, as it was a totally new field of biology called organ-on-a-chip. I then pushed my knowledge on several organs cultured during ex vivo experiments during my PhD.
By sharing the conviction that organ-on-a-chip technology will be the next generation of in vitro devices, I joined Cherry Biotech’s R&D team. I am using my knowledge in physiology, toxicology, biology and organ culture to develop innovative devices dedicated to organ-on-a-chip technology.
R&D Project Manager
This article appears in issue two of Pan European Networks: Health, which is now available to read online.