Periodic Reporting for period 2 - EUROoC (Interdisciplinary training network for advancing Organ-on-a-chip technology in Europe)
Periodo di rendicontazione: 2020-12-01 al 2023-05-31
Organ-on-Chip (OoC) technology is rapidly advancing due to its potential impact on drug development and personalised disease treatments. Researchers entering the field must be equipped with a multidisciplinary background ranging from cell biology and toxicology to biomaterial and microsystem engineering. EUROoC offered the first complete and coherent European training program by gathering multidisciplinary participants (biologists, physicists, chemists, engineers) in a multi-sectoral network composed of 8 companies (7 SMEs), 2 regulation entities, and 14 academic institutions. At the initial stage of the program, 15 early-stage researchers (ESRs) were recruited and trained in all aspects of OoC development and utilisation. EUROoC furthermore comprised a collection of innovative research projects addressing the development of advanced OoC systems with higher physiological significance going beyond current state of the art. During the program, each ESR developed a fit-for-purpose OoC and readout methodologies based on their individual project. This was achieved by extensive collaboration between ESRs and partner organisations. EUROoC successfully created advanced OoCs, which closely recapitulate properties of the respective organ tissues (heart, fat, liver, gut, & lung) in vivo regarding cell types, microenvironment, organ-specific tissue structure, and function as well as concepts for the interconnection of individual OoCs. The developed systems enable monitoring & analysing tissue functionality and response in situ by integrating novel sensing elements as well as novel microscopic techniques. At the end of the program, under the guidance of the regulatory partners, the developed OoCs were validated against currently established in vitro methods as well as through comparison with in vivo literature data. The research and training program proved to increase European competitiveness sustainably in this emerging key technology.
The EUROoC consortium was created with the aim of bringing together academia, industry, and governmental agencies to collaboratively advance the development and regulation of OoC. A comprehensive project management framework was implemented, encompassing the establishment of boards & committees, meeting formats, and reporting guidelines. Various dissemination channels, such as the project website, a Twitter & LinkedIn account, and the project newsletter were established. Throughout the recruitment process, all ESR positions were filled, achieving a gender balance of 64% women to 36% men. To date, 3 ESRs have successfully defended their PhDs and most others are finalising thesis writing or have already submitted their theses. Over the course of the consortium, ESRs were actively engaged not only in their individual projects but also in outreach activities, including the creation of videos showcasing their projects and promoting the shared objective of OoCs within the 3R (replacement, reduction, refinement of animal testing) framework.
Despite the major impact of the COVID-19 pandemic, the ESR research endeavours progressed according to plan, with minor adjustments necessitated. Notably, results were published concerning the development of heart-on-chip models using human stem cell-derived cardiomyocytes, endothelial cells, & cardiac fibroblasts. Additionally, barrier-on-chip models for the retina, lung, gut, and microvasculature were created. The integration of optical sensors for pO2, pH, and glucose, along with bead-based assays for cytokines, into various OoCs allowed for real-time monitoring of changes in cell metabolism & culture conditions in minute sample volumes and the results were published in several scientific journals. Advanced metabolising OoC models for gut, liver, and white adipose tissue were established.
Despite the major impact of the COVID-19 pandemic, the ESR research endeavours progressed according to plan, with minor adjustments necessitated. Notably, results were published concerning the development of heart-on-chip models using human stem cell-derived cardiomyocytes, endothelial cells, & cardiac fibroblasts. Additionally, barrier-on-chip models for the retina, lung, gut, and microvasculature were created. The integration of optical sensors for pO2, pH, and glucose, along with bead-based assays for cytokines, into various OoCs allowed for real-time monitoring of changes in cell metabolism & culture conditions in minute sample volumes and the results were published in several scientific journals. Advanced metabolising OoC models for gut, liver, and white adipose tissue were established.
OoC technology has been widely recognised to hold the potential to be the next decade’s game changer the pharmaceutical industry has been looking for. However, its socio-economic impact extends beyond this sector, offering the potential to significantly reduce reliance on animal testing. Presently, OoCs are primarily utilised in laboratories of developing researchers, highlighting the need for increased collaboration among academia and non-academic stakeholders. EUROoC focused on creating novel OoC systems with controlled mechanical properties for heart and bone, recognising the pivotal role of mechanical loading in their structure & function. The project's achievements encompassed the development of 3D bone and heart tissues that incorporated human stem cell-derived cell types. The effects of mechanical load on these systems were evaluated through techniques such as electrophysiology, force & contraction sensing, and imaging. Barrier-on-chip models for retina, lung, gut, and microvasculature were developed, featuring integrated sensors for real-time monitoring. These models enabled the observation of changes in cell morphology and culture conditions in minute sample volumes. Four disease models were developed and subjected to rigorous analysis of inflammatory markers. EUROoC also pioneered the modelling of white adipose tissue-on-chip, achieving a glucose-sensitive & hormone-responsive model with integrated sensors for real-time monitoring. A sensor array was developed to track metabolic cell markers online, enhancing monitoring efficiency. The project successfully validated a reproducible immune response in the liver model to microbial-associated molecular pattern stimulation and achieved co-culture of immune cells in the adipose tissue on-chip. A significant accomplishment was the establishment of the microbial crosstalk interconnected with a liver model. An infection model with circulating immune cells was integrated into the liver-on-chip model, opening new avenues for studying metabolic diseases through a bioenergetic interconnection.
Despite the challenges posed by the pandemic, EUROoC significantly advanced OoC technology and played a crucial role in strengthening cooperation between academia, industry, and regulatory agencies. It provided a sustainable training program across Europe through workshops and ongoing promotion of training opportunities, even beyond the project's completion. EUROoC also contributed to enhancing the innovation capacity of EU Member States by instilling an entrepreneurial mindset in young researchers, providing them with skills to drive meaningful innovations, thereby contributing to the sustainability of European growth and competitiveness. The developments facilitate the monitoring & analysis of tissue functionality and responses, achieved through the integration of novel sensing elements and pre-validated through in vitro-in vivo correlations.
Particularly noteworthy is the importance of the project for the training of the ESRs involved. The programme successfully provided its ESRs with interdisciplinary skills. In the final stages of their projects, guided by regulatory partners, ESRs addressed aspects of drug metabolism in their investigations. They also gained valuable insights into validation for in vitro & in vivo models. The project successfully trained mobile researchers with key skills, preparing them for future leadership roles in OoC research & innovation. They are now capable of establishing and pre-validating novel OoC platforms that can be easily transferred to end-users.
Despite the challenges posed by the pandemic, EUROoC significantly advanced OoC technology and played a crucial role in strengthening cooperation between academia, industry, and regulatory agencies. It provided a sustainable training program across Europe through workshops and ongoing promotion of training opportunities, even beyond the project's completion. EUROoC also contributed to enhancing the innovation capacity of EU Member States by instilling an entrepreneurial mindset in young researchers, providing them with skills to drive meaningful innovations, thereby contributing to the sustainability of European growth and competitiveness. The developments facilitate the monitoring & analysis of tissue functionality and responses, achieved through the integration of novel sensing elements and pre-validated through in vitro-in vivo correlations.
Particularly noteworthy is the importance of the project for the training of the ESRs involved. The programme successfully provided its ESRs with interdisciplinary skills. In the final stages of their projects, guided by regulatory partners, ESRs addressed aspects of drug metabolism in their investigations. They also gained valuable insights into validation for in vitro & in vivo models. The project successfully trained mobile researchers with key skills, preparing them for future leadership roles in OoC research & innovation. They are now capable of establishing and pre-validating novel OoC platforms that can be easily transferred to end-users.