MICA: Organ-on-a-chip models for safety testing of regenerative medicine products

Regenerative medicine aims to replace or regenerate human cells, tissues or organs to restore or establish normal function. Any newly developed products much be subject to stringent pre-clinical safety tests before use in humans. Currently, we mainly use animal models for pre-clinical safety testing, but not only does this bring ethical concerns, but animals are biologically different to humans, so sometimes the testing can provide poor indication of the product is actually safe in humans. We urgently need more representative models which contain human cells, to see how our bodies will react to the new products.

Our project is focused on the design of new, improved models for the predictive safety testing of new regenerative medicine products. The models we will create are called "organ-on-a-chip" models, as they create a miniature biologically correct human organ on a small device reminiscent of a computer chip. We can input the new regenerative medicine products into the organ of choice built onto the chip, to see how that organ will respond.

We will work one of the largest manufacturers of organ-on-a chip models, a company called Emulate Inc. They have already created organ-on-a chip models of lung and liver which we will establish in our laboratories, before we create brand new models of the different musculoskeletal tissues prone to injury, so we can test new regenerative medicine products developed for any of these tissues.

Working with Emulate is important as they have developed a commercially available platform within which we can develop the models, making it easier and faster to translate our new models to commercial products, available to all companies, clinicians and researchers trying to create new drugs or regenerative medicine products.

This project aims to support the ECE Hub by developing new robust, validated predictive models for the pre-clinical safety testing of regenerative medicine products. We focus on organ-on-a-chip approaches, and collaborate with one of the largest commercial company in the field, Emulate Inc., specifically to address the needs for reliability and control in a scaleable manner in new predictive models. We additionally engage with the regulatory bodies to support the integration of our predictive models into the regulatory framework for pre-clinical safety testing.

Working directly with the Engineered Cell Environment Hub, our goals are to develop and validate new organ-on-a-chip models of each ECE Hub clinical focus area; liver, lung and joint.

We will establish models within the Emulate platform technology (The Human Emulation Platform) phenotyping to ensure appropriate recapitulation of the organ on interest. We will carry out mechanistic safety testing in models, inputting drugs known to cause toxic effects in the organ in vivo, to ensure the organ-on-a-chip model can recapitulate that response. With appropriate validation in place, we will test some initial regenerative medicine products for the ECE Hub, working with the Edinburgh Phenotypic screening centre to align the drug libraries to those selected by the ECE Hub.

We will also begin work on pathological models of organs within the organ-on-a-chip devices, to recapitulate situations in which the drug or product must be administered to a pathological organ.

This strongly industrially-linked proposal trains a team of 3 new researchers in the field of organ-on-a-chip models. We will develop new predictive models for testing regenerative medicine products on an industry-ready platform, bringing regulatory bodies within the steering group, to facilitate the translation of organ-on-a-chip approaches to pre-clinical safety testing.

Clinical impact from organ-on-a-chip technology arises from its implementation to facilitate more effective and rapid pre-clinical safety testing of drugs and products across the regenerative medicine field and wider. However, newly developed organ-on-a-chip models can also help us to understand healthy tissue function and the aietiology of disease, as recapitulation of physiology and pathology necessitates investigation and subsequent insight into the drivers of these processes.

There is also a clear route to impact in personalised medicine, as organ-on-a-chip models can easily by personalised (using a patients' own cells) which provides exciting clinical opportunities to interrogate and optimise individualised treatment plans.

The development of organ-on-a-chip models tackles a very significant current bottleneck in the development of new drugs and medical products, offering clear economic input associated with the cost reduction involved in bringing new drugs or regenerative medicine therapies to market and subsequently in treating illness, bringing streamlined processes and fewer late stage failures of new products in clinical trials.

Models bring large scale opportunity for commercial impact also, arising from commercialisation of the new OOAC models we develop, and also from their subsequent use to develop new regenerative medicine products or drugs for treating disease or injury.