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Extracellular Vesicle-Inspired CArdiac Repair

Objective

More than 3.5 million people are newly diagnosed with heart failure every year in Europe with a long-term prognosis of 50% mortality within 4 years. There is a major need for more innovative, regenerative therapies that have the potential to change the course of disease. My hypothesis is that we can recondition heart failure by stimulating cardiac repair with extracellular vesicles that are derived from progenitor cells. In my laboratory, extracellular released vesicles containing a cocktail of stimulating factors, are amongst the most potent vectors for cardiac repair.
To achieve a sustainable and long-term therapeutic effect of these vesicles and enhance cardiac function by stimulating myocardial repair, we will 1) improve local cardiac delivery of progenitor cell-derived extracellular vesicles, 2) understand the mechanism of action of extracellular vesicles, and 3) stimulate extracellular vesicles release and/or production by progenitor cells.
These questions form the rationale for the current proposal in which we will co-inject extracellular vesicles and slow-release biomaterials into the damaged myocardium. By subsequent genetic tracing, we will determine fate mapping of injected vesicles in vivo, and perform further mechanistic understanding in in vitro culture models of targeted and identified myocardial cell types. Moreover, we will upscale the vesicles production by progenitor cells further via bioreactor culturing and medium-throughput screening on factors that stimulate vesicles release.
The use of stem cell-derived extracellular vesicles to stimulate cardiac repair will potentially allow for an off-the shelf approach, including mechanistic understanding and future clinical use. Additionally, since these vesicles act as a natural carrier system outperforming current artificial drug delivery, we might understand and mimic their characteristics to enhance local (RNA-based) drug delivery systems for cardiovascular application.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 997 297,99
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 997 297,99

Beneficiaries (1)

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