The Project
EVEStemInjury is a European scientific project about the use of Extracellular Vesicles and exosomes from adult stem cells for the regeneration of organ injury.
The project EVEStemInjury is granted by the European program FP7-PEOPLE-2013-IAPP – Marie Curie Action: “Industry-Academia Partnerships and Pathways” (IAPP).
EVEStemInjury project is currently coordinated by Bioindustry Park Silvano Fumero SpA.
Purpose
The EVEStemInjury project aims to explore the role of Extracellular Vesicles (EVs) as new potential therapeutic strategies in the field of regenerative medicine, with a special focus on acute and chronic kidney disease.
For further details:
Acute and chronic kidney disease is a worldwide problem and the large part of the bad outcome of end-stage renal disease (ESRD) patients is due to deficient follow-up during the earlier chronic kidney disease (CKD) stages.
The scientific community fully agree on the role of extracellular vesicles and exosomes (EVs) in modulating target cells phenotype promoting regeneration of injured cells by transferring specific extracellular RNAs (mRNA, miRNAs and long non-coding RNAs) that they operate through paracrine/endocrine mechanisms rather than permanent engraftment and trans-differentiation of stem cells.
Within the project, we are:
- extensively characterising EVs involved in kidney and liver injury regeneration;
- exploring their mechanisms of action in healing tissue injury;
- defining the most promising EVs’ “active biological ingredients”, both at molecular and protein level;
- exploring two different approaches of EV production: Biological and Synthetic, in order to evaluate their feasibility and assess their efficiency;
- assessing the renoprotective effect of EVs, using in vitro and in vivo models of acute kidney injury;
our final goal is to further promote the identyfied EVs as new potential therapeutic strategies in the field of regenerative medicine.
Work Packages
In order to achieve the final goal, the EVEStemInjury project has been organized into seven different technical and managerial work packages.
1. Definition of biological ingredients
Description of the work:
- Identification of the optimal “RNA Healing” shuttled by vesicles (EVs) derived from different adult stem cell sources and generation of engineered EVs.
- Analysis of different EV population by density gradient.
- Definition of the effects of EVs on the phenotype profiles of injured renal cells which have been restored by exposure to BM- MSC, ASC or HLSC-derived EVs.
Leading group: Bioindustry Park (M25-48)
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2. Mechanisms of actions
Description of the work:
The objectives of this WP will be achieved by performing the two following activities:
- Identification of specific EV-derived proteins important in conferring renal protection.
- Strategy to engineer EVs derived from plasma and serum.
Leading group: London Metropolitan University (LMU)
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3. EV production strategies
Description of work:
A synthetic version of EV that only contains the minimal components needed, will be explored. To this minimal formulation, compounds can be added to see whether it significantly improves the efficacy (bottom-up approach). Additionally, we will work with natural EV and subsequently bio-engineer these vesicles in order to enhance their pharmacological activity and to loose unwanted effects (top-down approach). The two following activities will thus be performed:
- Synthetic production of EV.
- Biological harvesting of EV.
Leading group: Universitair Medisch Centrum Utrecht (UMCU)
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4. Renoprotective and regenerative effects assessment
Description of work:
The two following activities will be performed:
- Study of the protective and regenerative effect of EVs and therapeutic RNAs in a mice model of chronic nephrotoxicity by Cyclosporine A (CsA)
- Study of the protective effect of EVs and therapeutic RNAs against the toxicity by immune-suppressors in a primary cell culture of human proximal tubular cells
Leading group: Consorci Institut d’Investigacions biomèdiques (IDIBAPS)
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5. Scientific communication and project management
Description of work:
The objectives of this WP is the training of the fellows. To reach this aim training events and workshops will organized.
Leading group: Consorci Institut d’Investigacions biomèdiques (IDIBAPS)
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6. Dissemination activities (increase of awareness in the researched field by general public)
Description of work:
The objectives of this WP is the dissemination of project results. To reach this aim the following activities will be implemented:
- Planning of outreach activities; set-up “Outreached Activities Plan” and Open Day sessions.
- Support of publication, dissemination activities and monitoring of IPR sensitive issues.
PUBLICATIONS:
- Apr 2014, Poster presentation at ISEV2014. “Evaluation of the renoprotective effect of murine bone marrow mesenchymal stem cells, EVs and conditioned medium in a model of chronic nephrotoxicity”, Maria Ramirez-Bajo.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001129/pdf/JEV-3-24214.pdf)
- Apr 2014, Poster presentation at ISEV2014. “Extracellular Vesicles and exosomes from adult stem cells in the regeneration of organ injury”, Federica Collino.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001129/pdf/JEV-3-24214.pdf)
- Oct 2015, Paper: AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs. Collino et al., J Am Soc Nephrol. 2015 Oct;26(10):2349-60. (http://jasn.asnjournals.org/content/26/10/2349.full.pdf+html)
PROJECT WEBSITE
- http://www.tcrm-unito.com/research-area/evesteminjury/
- http://www.bioindustrypark.eu/evesteminjury/ from the 3rd year of the project
Leading group: Bioindustry Park (M25-48)
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Partner
Bioindustry Park Silvano Fumero is a science and technology park located in Canavese, near Turin in the north of Italy. The Park promotes and develops research in Life Sciences, hosting companies of the chemical, pharmaceutical, diagnostic, bioengineering and information science fields. It has acted as system integrator for the development of Life Sciences in Piemonte since its creation in 1998. Moreover, Bioindustry Park is the “managing company” that coordinates bioPmed cluster, dedicated to healthcare, sound, dynamic and competitive, able to interact with the healthcare system, open to dialogue with the citizens and recognized at local, national and international level.
ROLE: Within EVStemInjury project Bioindustry park replaced Fresenius in data and is in charge of EVStemInjury project coordination and leading WP1, WP6 and WP7 activities.
Fiorella Altruda
PhD
President of Bioindustry park Silvano Fumero SpA – B.i.P.Ca. S.p.A.
Fiorella Altruda is Full Professor of Molecular Genetics at Molecular Biotechnology Center – Department of Molecular Biotechnology and Health Science.
One of her current research focuses on stem cells and regenerative medicine, with special attention to the use of stem cells for the cure of liver diseases.
Alberto Baldi
Cluster Coordinator of bioPmed Piemonte Healthcare Cluster and Business Development & International Projects of Bioindustry Park Silvano Fumero S.p.A. – Bi.P.Ca. S.p.A.
Alberto Baldi focuses his activity on Cluster management and strategic development of bioPmed Piemonte Healthcare Cluster. He’s also involved in marketing and promotion of the “Bioindustry Park System” (science park, incubator, R&D labs, regional healthcare cluster management company) and of the entire regional Life Sciences sector.
The London Metropolitan University houses the Cellular and Molecular Immunology Research Centre (CMIRC) which is dedicated to EVs and exosomes research, working exclusively on the various roles of EVs in autoimmune disease, cancer and infection. More specifically, they have expertise in 2D-Difference Gel Electrophoresis and proteomic analysis of MVs.
ROLE: Within EVStemInjury project LMU is in charge of leading WP2 activities and contribute to WP5 and WP6.
Jameel Inal
PhD
London Metropolitan University (LMU)
Cellulare & Molecular Immunology Research London, UK
Jameel Inal is Professor of Immunology and Director of the Cellular and Molecular Immunology Research Centre.
His research activities are focused on immunology, plasma membrane-derived vesicles, Synthetic peptide design for complement inhibition and Complement regulation by host and parasite.
The Universitair Medisch Centrum Utrecht (UMCU) is one of the largest public healthcare institutions in the Netherlands. Its Laboratory Clinical Chemistry & Hematology is, among others, specialized in nanoparticle characterization as well in manufacturing of synthetic and biologically engineered EV mimics.
ROLE: Within EVStemInjury project UMCU is in charge of leading WP3 activities and contribute to WP5 and WP6.
Raymond M. Schiffelers
PhD
Universitair Medisch Centrum Utrecht (UMCU)
Laboratory Clinical Chemistry & Hematology Utrecht, NL
Raymond Schiffelers is Professor of Nanomedicine at the Universitair Medisch Centrum Utrecht (UMCU).
One of his current research interests is natural and synthetic nanoparticles for diagnosis and therapy.
The Institut d’Investigacions Biomèdiques owns the Experimental Laboratory of Nephrology and Transplantation (LENIT), a multi-disciplinar laboratory developing several research lines focusing in native and allograft kidney diseases, acute and chronic renal failure and renal cancer. IDIBAPS has a consolidated experience on studies devoted to the pathogenic mechanisms associated to chronic transplant nephropathy and the nephrotoxicity associated to anti-calcineurin inhibitors.
ROLE: Within EVStemInjury project UMCU is in charge of leading WP4 and WP5 activities and contribute to WP6.
Dr. Fritz Diekmann
PhD
Institut d’Investigacions Biomèdiques, IDIBAPS
Experimental Laboratory of Nephrology and Transplantation (LENIT)
Fritz Diekmann is staff member in Renal Transplant Unit at Hospital Clinic IDIBAPS, Barcelona.
His main research interests are immunosuppressive strategies after kidney transplantation, especially in expanded criteria donor kidney transplantation as well as in hypersensitized kidney transplant patients.