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Mimicking organs on chips for high throughput drug screening and basic research

Periodic Reporting for period 2 - MIMIC (Mimicking organs on chips for high throughput drug screening and basic research)

Reporting period: 2018-01-01 to 2019-12-31

Development of novel drugs is a costly and time-consuming process. Often years of investments are lost as it turns out that the drug candidate is toxic to humans or does not have the effects observed previously in simple cell culture test in patients. Drug candidates are usually also tested in animals, however given species differences the behaviour of a drug candidate in animals is not always a good predictor for its behaviour in humans. Animal testing bears also several ethical issues as it might heavily impact on animal welfare. Thus there is a high demand in the pharmaceutical industry to have more reliable early test systems.
Organ on chip technology is a recent research & development area aiming at mimicking organ functionality in microfluidic systems. This technology allows the modelling of certain tissue/organ features using spatially defined culturing of cells usually under flow mimicking for example blood flow or air flow (for example in a lung on chip). In particular, organ on chips are ideally suited to establish the spatially defined co-culturing of different cell types, which increase the complexity significantly compared to standard 2D or 3D cell cultures. Thus organ on chip technology might be able to close the currently existing gap for more reliable test models for the pharmaceutical industry.
The ITN-MIMIC represents an international research consortium between academic partners and industry with a joint interest to further develop organ on chip technology and to exploit this technology for efficient drug development and basic research.
MIMIC focuses in particular on the further developments of two organ on chip models, which is a kidney on chip model and a gut on chip model. Aim of MIMIC is to develop models for these organs, which are suitable for high-content drug screening. Furthermore, using state of the art genetic engineering tools (CRISPR) and modern stem cell differentiation protocols MIMIC aims to develop specific disease models for the kidney and gut, by genetically engineering cell lines harbouring patient mutations known to cause disease. These models have been used to investigate disease mechanism in more detail but also to identify potential drug candidates and drug targets to treat the disease.
Conclusions: MIMIC has successfully trained four early stage researchers in the framework of a tailored MIMIC training programme and a local PhD programme in the field of organ on chip technology suitable for high-throughput drug screening. All ESRs have submitted their PhD thesis or are close to submit it. Furthermore, MIMIC has successfully established novel human in vitro disease models for inflammatory bowel disease and Lowe syndrome suitable for drug and drug target screening. MIMIC has performed a number of outreach activities raising in particular awareness for the emerging technology of organ on chip technology, including questions of animal welfare consideration in research and challenges of modern drug development as well as joint European research in general.
MIMIC started with its kick-off meeting in Leiden, Netherlands where the partners came together to discuss the recruitment strategy and other organisational matters. The first training event for the fellows was a fellow-own meeting organised by the fellows themselves. This meeting took place in Sheffield/York, UK. The fellows invited two external speakers and MIMIC logo, Facebook and Twitter account were established. Annual meetings of MIMIC were held in Leiden, Netherlands, where fellows reported on their individual project progress and further collaborations between partners were outlined. MIMIC fellows have also attended a workshop I: ‘Bioethics and Advanced Communication skills’ and performed at least three experimental training stations to acquire expertise in certain techniques provided by the consortium. MIMIC has organised a total of four workshops as well as a MIMIC school and a final scientific meeting. Workshop II (Project Management, Innovation & Creativity for Research) was run in January 2018 in Sheffield. The purpose of this workshop was to provide fellows with the opportunity to learn about the process of creativity and innovation. A MIMIC school was organised as an event comprising “Organ-on-a-Chip Technologies Network Learning and Collaborative Event 2019” and the ITN-MIMIC school “Mimicking organs on chips for high throughput drug screening and basic research” in April 2019 in London. Workshop III (Mini-MBA) was run in two parts, where the first part was prepared and run as webinars. All MIMIC ESRs took also part in the BioYES (Biotechnology YES) business plan competition 2018. BioYES (Biotechnology YES) is an innovative competition designed to develop business awareness and an understanding of entrepreneurship in postgraduate students and postdoctoral researchers. Our MIMIC fellows won the price for best intellectual property strategy. Workshop IV – Career Development was run in August 2019 in Leiden, the Netherlands. The final scientific conference, which took place in June 2019 in de Doelen Conference Center in Rotterdam in the Netherlands allowed MIMIC fellows to present their scientific data to a broad scientific community.
Overview of results and dissemination:
MIMIC has established successfully novel 3D in vitro models for inflammatory bowel disease and Lowe syndrome suitable for drug and drug target screening. A gut on chip model and a variation of this model mimicking the inflamed gut have been published in peer reviewed journals. Fellows have presented their research at a total of six international meetings in the form of posters. Furthermore, there are currently three additional publications with MIMIC fellows as first author in preparation.
Currently, MIMIC has led to two peer reviewed publications. The content of the first publication describes the first gut on chip model established on OrganoPlates suitable for high-throughput drug screening. This publication might have a major impact on drug screening strategies of pharmaceutical companies, who might apply the published organ on chip model in their drug development programs. In the second publication we have capitalised on the first publication developing a model for inflammatory bowel disease. Here we have presented proof-of principle data, that this model is suitable for drug and drug target development in inflammatory bowel disease research. Both publications have extended the current state of the art by presenting 3D disease models suitable for drug screening and are thus of potential interest for the pharmaceutical industry. The models are also allowing to study disease mechanism in an easily accessible and reproducible manner.
We believe that our scientific findings have the potential to improve efficiency of the drug screening process by reducing time and costs and will contribute to replace at least in part the use of animals, however further research and development in the emerging research area of organ on chip technology is necessary.
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