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Optimizing the human perinatal progenitor cell secretome for future paracrine therapy to counteract cardiac disease with AmnioSMART: an ERA4Health-funded project

Year: 2024
Type: article
Abstract: The EU-funded Partnership ‘Fostering a European Research Area for Health’ (ERA4Health) is a programme bringing together 33 institutions from different countries, including 17 out of the 27 members of the EU, and 5 Third Countries (from which 3 are associated to Horizon Europe). The main aim of the ERA4health is to regularly sponsor international joint calls for proposals aimed at developing breakthrough collaborative research joint strategies to address current unmet clinical needs and thus reduce disease burden across Europe (source: https://era4health.eu/at-a-glance). Among the different funding opportunities, the 2023 ERA4Health framework focused on innovative, yet feasible, treatments for cardiovascular disease with specific translational potential, as per the main goal of the call: ‘Research targeting development of innovative therapeutic strategies in cardiovascular disease (CARDINNOV)’. Being one out of the 17 funded proposals, the AmnioSMART project aims at the development of a cell-derived, yet cell-free, approach in combination with bioactive smart biomaterial formulations to tackle cardiac disease and counteract myocardial dysfunction. The AmnioSMART project is about ‘Defining the ideal human Amniotic progenitor Secretome forMulation for future cArdioprotective paRacrine Therapy’. The analysis of the cellular cross-talks within the myocardial microenvironment has gained increasing attention as a promising therapeutic target to enhance clinically relevant mechanisms of endogenous repair, including quenching exacerbated inflammation, while preserving functional cardiomyocytes and limiting fibrosis. AmnioSMART will unite internationally renowned researchers from Italy, Portugal, Belgium, and the Netherlands to define an investigational novel treatment ensuring medium-to-long-term paracrine effects; in such a perspective, secretome formulations obtained from human amniotic progenitor cells with cardioportective effects will be delivered to the heart using smart biomaterials optimized to present an adequate controlled delivery in order to be further exploited in compliance with the cardiovascular patient’s needs. Prof. Sveva Bollini, AmnioSMART Coordinator, from IRCCS Ospedale Policlinico San Martino in Genoa (Italy), and Prof. Ornella Parolini, AmnioSMART Partner from Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome (Italy), have previously demonstrated that developmentally immature perinatal stromal progenitors from the human amniotic fluid and the amniotic membrane possess remarkable cardioprotective and immunoregulatory potential, respectively, thus representing appealing sources of secretome-based therapeutics for future paracrine therapy. The AmnioSMART Consortium will also include Prof. Rui Reis and Dr Ricardo Pires from the University of Minho, Braga, Portugal as major experts in smart delivery systems with advanced state-of-the-art biomaterials. The expertise of Prof. Maurilio Sampaolesi, from KU Leuven, Leuven, Belgium, and Dr Monika Gladka from Amsterdam University Medical Centers, Amsterdam, the Netherlands, will refine cardiac modelling platforms for functional validation of the therapeutic formulations. AmnioSMART proposes an interdisciplinary and integrative approach based on the synergic and complementary expertise of the Consortium Partners (Figure 1) by combining perinatal progenitor paracrine biology with functionalization of smart biomaterials, along with 3D tissue engineering and advanced modelling for cardiac disease, in order to implement technology transfer into the clinical scenario. The panel on the left represents the AmnioSMART Consortium with representatives and team members from each partner unit. Photo taken during the project kick-off meeting in May 2024 at IRCCS Ospedale Policlinico San Martino in Genoa, Italy. The schematic on the right highlights the interdisciplinary and synergistic combination of expertise within the AmnioSMART project The project has the potential to generate significant impact from the following perspectives. Health and clinical impact: the AmnioSMART will develop a therapeutic platform while addressing cardiovascular patient compliance. The project will refine cardioprotective secretome-based products suitable for patients at risk of heart failure (including acute myocardial infarction and inflammatory or cardiotoxic cardiomyopathy), thus maximizing clinical impact. Furthermore, this innovative strategy based on the collaboration among multidisciplinary experts, combination of cutting-edge technologies, and iterative testing will provide the basis for product development and future market entry. Scientific and methodological impact: the AmnioSMART will also offer new insights into the cardioprotective and anti-inflammatory roles of the whole cell-secretome vs. specific sub-fractions, such as the extracellular vesicle component. Additionally, the project will optimize formulation composition and manufacturing. Socio-economic impact: the AmnioSMART Consortium will develop technological solutions to improve the production process of therapeutic formulations, thus fostering biotechnology applications. All authors declare no disclosure of interest for this contribution. This project received funding from the Italian Ministry of Health in Italy, by the Portuguese Foundation for Science and Technology (CARDINNOV/0001/2023) in Portugal, by the Research Foundation—Flanders in Belgium and by The Dutch Research Council in the Netherlands under the umbrella of the Partnership Fostering a European Research Area for Health (ERA4Health) (GA N° 101095426 of the EU Horizon Europe Research and Innovation Programme) (CARDINNOV call text). The AmnioSMART Consortium: Sveva Bollini (Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy); Ornella Parolini (Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy), Rui L. Reis (3B's Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal; ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal), Ricardo A. Pires (3B's Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal; ICVS/3B's–PT Government Associate Laboratory, Braga/Guimarães, Portugal), Maurilio Sampaolesi (Department of Development and Regeneration, Stem Cell and Development Biology Unit, KU Leuven, Leuven, Belgium; Histology and Medical Embryology Unit, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Sapienza University of Rome, Rome, Italy), and Monika M. Gladka (Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, The Netherlands).
Language: English
Subfield: Genetics
Field: Medicine
Open Access status: green
OpenAlex ID: W4403464181
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