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The Extracellular Vesicle Foundry

Periodic Reporting for period 2 - evFOUNDRY (The Extracellular Vesicle Foundry)

Reporting period: 2019-09-01 to 2022-02-28

Extracellular vesicles (EVs) are nanoparticles produced by cells in order to delivery specific massages to other cells. To study their structure and content can be exploited to improve fundamental aspects of everyday life, from diseases diagnosis and therapy to environment and public health. However, EV understanding and manipulation ability are immature. evFOUNDRY aims at advancing EV field by developing a technology that streamlines the production of EVs from sustainable sources (milk and parasitic worms). This is necessary for an effective medical application of EV-based products and opens to new EV applications: for example, EV can be used as food supplements or added to cosmetics to improve their efficacy or used in veterinary.
evFOUNDRY specific objectives are:
1) to produce pure, stable and reproducible sets of nanosized EVs from bovine milk and Ascaris suum, a parasite present in the gut of pigs;
2) to understand the interaction of EVs with lipid membranes and exploit it to develop innovative, high-performance materials for the purification of EVs from the starting source;
3) to design and fabricate a device for automatic purification of EVs.
All the planned activities are within three established main actions:
- Action 1. EV quality standards set, including: (1) purification of EVs from bovine milk and Ascaris suum incubation media. These fluids are very attractive “infinite” sources of EVs because they are cheap, widely available, sustainable and ethically compliant and their EVs have biological activity and medical potentiality; (2) set up of methods and workflow for determination of (a) chemical properties and (b) of the biological properties of the purified EVs.
- Action 2. Materials and methods development for efficient purification of nanosized EVs that work under continuous flow. Delivered results include:
(a1) a device able to pre-process the starting source to remove unwanted material that can modifying properties and functions of the EVs;
(a2) a device based on deterministic lateral displacement (eDLD) that separate EVs for size;
(b) the understanding of interactions between EVs and lipid membranes. Results can potentiate the two devices performances, mimicking the interaction with cellular membranes.
- Action 3. Realization of an integrated device (a1+a2) for augmented purification of EVs.
Due to COVID-19 pandemic restrictions, not all the testing could be replicated as planned, however obtained results gave positive indications regarding feasibility and advantage – in terms of yield, biological properties of the products and costs – of evFOUNDRY device use as a component in large-scale purification processing. This puts the bases for next exploitation of such evFOUNDRY for large-scale EV manufacturing.
The whole consortium has been very active in communicate the project results using different channels to reach the widest audience.
Some of the most important actions regard the publication of more than twenty articles on peer review scientific journals with more than five featured the cover of international journals. The organization of the International Society of Extracellular Vesicles (ISEV) workshop “MassivEVs” on EV large-scale production and an intense participation to international meetings with more than sixty contributions.
The involvement in sixteen cluster events with other related European and international projects and the organization/participation to several training workshops on the (or inspired by) the project featured science and technology.
Results obtained by the technical actions described above impacted on the society and the scientific community. Research quality and EV community awareness on evFOUNDRY topics regarding large-scale production and EV manufacturing highly increased.
It is to note that each partner involved in evFOUNDRY hired young researchers (nine persons, from Ph.D students to Post-Docs). Their skills and enthusiasm fundamentally contributed to reach project’s goals.
In addition, the experience acquired and consolidate during the project allowed many of the young researcher to advance in their career and to find a new job both in academia and in private companies. In particular, two post-docs started a new career in industries, one as software engineer and one as process supervisor engineer. Two post-doc decided to continue their academic career applying to different grants for an independent position or entering to a tenure track position in different universities. Some young researchers involved in evFOUNDRY are now involved also in the FET-PROACTIVE project Biogenic Organotropic Wetsuits (BOW, Nº 952183) and their experience will be useful for the advancement of the new project. Ph.D students will defend their thesis in the next months and most of them already found post-doc positions in new universities of the European countries. evFOUNDRY was also a platform to the academic world: some collaborators decided to start a Ph.D programme after their involvement within the project.