Microbioreactor platforms as in vivo-like systems to probe the role of Neuroblastoma-derived Exosomes in cancer dissemination

Informations projet

MICRONEX

N° de convention de subvention: 759467

DOI

10.3030/759467

Projet clôturé

Date de signature de la CE 12 Septembre 2017

Date de début 1 Decembre 2017

Date de fin 30 Novembre 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 446 250,00

Contribution de l’UE

€ 1 446 250,00

Coordonné par

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 4 - MICRONEX (Microbioreactor platforms as in vivo-like systems to probe the role of Neuroblastoma-derived Exosomes in cancer dissemination)

Période du rapport: 2022-06-01 au 2023-11-30

Résumé du contexte et des objectifs généraux du projet

MICRONEX aimed to address the limitations of standard laboratory practices in studying cancer, particularly Neuroblastoma (NB), a pediatric tumor. The project focused on developing advanced microscale technologies to better mimic the complex tumor microenvironment and understand the role of extracellular vesicles (EVs) in tumor progression.
NB is the most common malignancy in early childhood; it is characterized by high biological heterogeneity, variable prognosis, and high tendency to metastasize. There are many unanswered questions and poorly understood phenomena around the mechanisms of EVs-mediated tumor communication and tumor progression, and we believe that the use of advanced technologies might be key in providing novel insights. The technological advances we sought to develop are defined microbioreactors (μBRs), small devices that exploit classical engineering principles for biomedical purposes.
Throughout the project, we developed devices specifically designed to respond to each biological question we posed. For example, we produced μBRs capable of generating time and space-resolved concentration gradients, support fast dynamic changes and reconstruct complex interactions between cells and tissues while performing multifactorial and parallelized experiments.
We are confident that our technological approach could be adapted and extended not only to studies of other types of human cancer, but also to several other biomedical applications.
The overarching goal of bridging the gap between in vitro techniques and in vivo biological phenomena, would undoubtedly help the scientific community in developing ever improving diagnostic tool and therapeutic protocols, ultimately greatly benefiting global health.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The project successfully achieved its objectives, resulting in several key technological and scientific advancements:

Characterization of NB-derived EVs:
We investigated the effects of EVs from hypoxic NB cells on tumor aggressiveness, identifying a miR-210-3p enrichment as a driver of metastatic behavior.

Development of Microscale Technologies:
We produced a microfluidic gradient generator (MGG) optimized for studying NB-derived EVs, enabling precise control over concentration gradients.
We integrated micropatterning within the MGG for high-throughput screening of EV-induced effects on protein expression levels.
We developed a two-photon polymerization (2PP) based device to study cell migration at single-cell resolution, revealing distinct behaviors of NB and mesenchymal stem cells (MSCs).

Innovations in Drug Delivery:
We engineered a microfluidic device for loading MSCs-derived EVs with Verteporfin (VP), a potential drug for NB therapy, demonstrating enhanced encapsulation efficiency and altered cellular response.

Advancements in 3D Models:
We developed bioinks and techniques for 3D bioprinting of vascularized constructs, facilitating the study of NB progression and metastasis in more physiologically relevant environments.

Establishment of Collaborations, Knowledge Transfer and Dissemination:
We collaborated with multidisciplinary teams, leading to joint publications and significant advancements in cancer research and drug development. We also engaged with industry partners for potential translational applications of the developed technologies. Our achievements were presented (oral or poster) in over 20 international conferences and led to 12 peer reviewed publications.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Throughout the action, we advanced the design and production of microscale technologies for studying cancer microenvironments and EV-mediated tumor progression. This approach demonstrated a strong translational potential through the established collaborations with research and industry partners.

The project's outcomes hold promise for improving cancer research methodologies, drug development, and personalized therapy approaches. The developed technologies and insights into NB progression pave the way for further advancements in understanding and treating not only pediatric cancers, but other cancers and diseases as well.

An overview of our technological solutions