Periodic Reporting for period 1 - GUTVIBRATIONS (GUT VIrus BRain Axis Technology In OrgaNoid Science)
Periodo di rendicontazione: 2021-04-01 al 2022-09-30
Over the last decade, several complex Organ-on-Chip (OoC) technologies have been developed, such as lung-on-chip, blood-brain-barrier (BBB) on chip and skin-on-chip. From an end-user perspective, the current iterations of OoCs are not user-friendly or do not have translation relevance. GUTVIBRATIONS (Gut Virus Brain Axis Technology In OrgaNoid Science) takes OoCs to the next level by using STACKS technology, organoid models, and Biosilk to develop a gut-brain axis organ-on-chip that mimics parts of the human body. The OoC that will be developed by GUTVIBRATIONS aims to provide an innovative solution for modeling human diseases and pre-clinical drug development. The key objectives within the GUTVIBRATIONS project are to develop a model that is easy to use, suitable for industrial purposes as well as applicable in the field of virology and beyond. By developing this next-level multi-organ system, GUTVIBRATIONS will fast track drug development that will minimize animal use, lower disease burden, and save lives.
GUTVIBRATIONS is divided into 10 Work Packages of which 6 are currently active. The work performed so far by the active Work Packages is as follows:
WP1 (BUILD): A method for producing biocompatible inserts designed for bio-silk has been developed. A standard operating procedure to functionalise inserts with silk nanomembranes and foam has been developed. The devices, reagents and methods have passed tests at end users labs.
WP2 (SHAPE): WP2 has focussed on developing a gut epithelial-mesenchyme co-culture. In this regard, a technique for patterning crypt-villi structures has been developed. Furthermore, successful co-culture of gut epithelial cells and fibroblasts has been achieved as well as a media for maintaining the cells in co-culture.
WP3 (DEFEND): We developed culture conditions that can support the co-culture of intestinal epithelial cells and immune cells on a defined extracellular matrix. In this co-culture system, epithelial cells form a polarized monolayer that shows specific expression of intestinal markers and confirms the acquisition of barrier functions. Similarly, dendritic cells added to the culture system express specific markers and demonstrate potential to trigger an immune response upon stimuli.
WP4 (SPREAD): We have already established many of iPSC-derived cell types necessary for BBB assembly such as astrocytes, pericytes and microglia. For these cell types we are currently testing the best laminin combinations to enhance cell marker expression. Additionally, we have also established in our laboratory a dorsal forebrain organoid model which will be used for the BBB-brain organoid co-culture.
WP9 (EXPLOIT): The GUTVIBRATIONS website and the communication, dissemination, and exploitation plans have been developed.
WP10 (MANAGE): A project management plan has been developed and several consortium meetings have been organized such as the Kick Off meeting, Prepare Meeting and the first Progress Meeting.
WP1 (BUILD): A method for producing biocompatible inserts designed for bio-silk has been developed. A standard operating procedure to functionalise inserts with silk nanomembranes and foam has been developed. The devices, reagents and methods have passed tests at end users labs.
WP2 (SHAPE): WP2 has focussed on developing a gut epithelial-mesenchyme co-culture. In this regard, a technique for patterning crypt-villi structures has been developed. Furthermore, successful co-culture of gut epithelial cells and fibroblasts has been achieved as well as a media for maintaining the cells in co-culture.
WP3 (DEFEND): We developed culture conditions that can support the co-culture of intestinal epithelial cells and immune cells on a defined extracellular matrix. In this co-culture system, epithelial cells form a polarized monolayer that shows specific expression of intestinal markers and confirms the acquisition of barrier functions. Similarly, dendritic cells added to the culture system express specific markers and demonstrate potential to trigger an immune response upon stimuli.
WP4 (SPREAD): We have already established many of iPSC-derived cell types necessary for BBB assembly such as astrocytes, pericytes and microglia. For these cell types we are currently testing the best laminin combinations to enhance cell marker expression. Additionally, we have also established in our laboratory a dorsal forebrain organoid model which will be used for the BBB-brain organoid co-culture.
WP9 (EXPLOIT): The GUTVIBRATIONS website and the communication, dissemination, and exploitation plans have been developed.
WP10 (MANAGE): A project management plan has been developed and several consortium meetings have been organized such as the Kick Off meeting, Prepare Meeting and the first Progress Meeting.
The current state-of-the-art in human disease modelling is the use of stem cell-derived organoids to capture human phenotype in vitro. Organoids, to a certain extent, recapitulate the physiology of the different human organs but don’t fully capture their complexity yet. In parallel, Organ-on-Chips (OoCs) have been developed by modelling some of the complexity of the different organ systems along the gut-brain axis, primarily using cell lines. Gut-on-chip models have become more complex, but do not have a major focus on the gut mucosa. In this respect, GUTVIBRATIONS goes beyond the state-of-the-art and will provide a new approach in modelling the gut-brain axis interaction with a focus on mimicking the human phenotype aspects of gut mucosa, BBB, and brain along the immune route. In addition, GUTVIBRATIONS’ mission is to maximize the exploitation of the gut-brain axis OoC along with the individual elements that make up the model such as STACKS, media and Biosilk. GUTVIBRATIONS impact strategy is to ensure widespread deployment of our OoC for disease modelling and pre-clinical drug development.
The expected impacts within and beyond GUTVIBRATIONS are as follows:
1) Verifiable progress in the application of OoC technologies for in vitro research
2) Reduction of the need for animals in clinical testing
3) Lowering of barriers for application of OoC technology
4) Improved competitiveness and attractiveness of the European bioemedical and healthcare sector.
5) Increased awareness and knowledge about medical regulatory policies and requirements, especially by academics and SMEs
The expected impacts within and beyond GUTVIBRATIONS are as follows:
1) Verifiable progress in the application of OoC technologies for in vitro research
2) Reduction of the need for animals in clinical testing
3) Lowering of barriers for application of OoC technology
4) Improved competitiveness and attractiveness of the European bioemedical and healthcare sector.
5) Increased awareness and knowledge about medical regulatory policies and requirements, especially by academics and SMEs