Periodic Reporting for period 4 - MINERVA (MIcrobiota-Gut-BraiN EngineeRed platform to eVAluate intestinal microflora impact on brain functionality)
Periodo di rendicontazione: 2021-11-01 al 2022-10-31
MINERVA final GOAL has been to develop the first engineered multi-organ platform recapitulating in vitro the connections among the main players of the MGBA: the gut microbiota; the gut epithelium; the immune system; the blood-brain barrier; the brain.
The PLATFORM relies on three compartments, one for each component of the axis, that host multiple units of an innovative, engineered organ-on-a-chip device, developed within MINERVA project, serially interconnected in order to represent the MGBA players’ interaction.
In the “Microbiota-compartment”, human microbiota strains can be cultured and produce a mix of molecules named “secretoma” that, once transported to the “Gut-compartment”, interacts with human gut epithelial cells and cells from the immune system, that modify it as occurs in vivo, giving the so-called “metabolised secretome”. It reaches the “Brain-compartment”, that hosts a complete Blood-Brain-Barrier model followed by two human brain cell models, where neurons, astrocytes and microglia, the three main cellular populations of the brain, can be: (a) co-cultured to explore microbiota effect on brain cells interconnected as in the real tissue; (b) cultured individually to investigate microbiota impact on each cell type.
A summary of the activities and main results follows.
We have selected the hydrogel formulations for neural 3D cell model development and optimised the protocols for neural cell culturing and biochemical assessment (WP1). We have set up the protocols for gut epithelium and immune system device exploitation (WP2) and set up the culturing conditions for microbiota strains, developing a new hydrogel formulation to model the gut intestinal mucus in the microbiota device (WP3). We have developed a highly versatile organ-on-a-chip device as “basic unit” to be tailored according to the requirement of the Brain device, Blood-Brain Barrier device, Gut epithelium device, Immune system device, and Microbiota device (WP1-3), and then we have functionally and biologically validated them (WP1-3). We have serially connected the organ-on-a-chip devices implementing MINERVA multi-organ platform, assessing its functional and biological performance once loaded with the in vitro models delivered before and characterised according to selected parameters (WP4). Finally, we have cultured the human microbiota collected from AD patients and healthy donors and allowed the resulting secretoma flow through the multi-organ platform loaded with the in vitro models obtained, and addressing brain cell response to the resulting healthy and neurodegenerative scenarios (WP5).
During the project lifetime, we have shared MINERVA aims and efforts with both the scientific community and the general public, implementing many open access peer-reviewed publications, several press release actions, reported also in social media, several dedicated pages on the Host Institution website. Furthermore, the setting-up ex novo of a dedicated “MINERVA” website, together with the participation to many scientific congresses and events targeting general public have also helped in sharing our main achievements (see www.minerva.polimi.it).
MINERVA is BREAKTROUGH: its new bioengineering APPROACH opens the way to a completely new FIELD at the boundary between neuroscience and engineering where the investigation of neurodegeneration causes can be shifted from the brain to the body periphery.
MINERVA has a potential HUGE IMPACT: its INNOVATIVE PLATFORM, thanks to its VERSATILE design, might address microbiota impact and therapeutic potential on brain but also not-brain centred diseases.
Finally, MINERVA represents by itself a major advancement in the field of multi-organ-on-chip devices but also in vitro brain disease models to explore new THERAPIES for brain disorders.