CARdiac Mesenchymal Extracellular Vesicles (CARMEV) for prevention of ischemic heart failure

Time period: 2019-04-01 to 2022-03-31

Project leader: Karl-Henrik Grinnemo

Funder: Vinnova

Type of award: Project grant

Total fundning: 4 191 500 SEK

Purpose and goal: The aim of this project is to develop a product called CARMEV, which is based on extracellular vesicles (EVs) from specific human prenatal cardiac mesenchymal stromal cells (hpcMSCs). These EVs are immunomodulating, inhibit apoptosis as well as stimulate angiogenesis, offering a direct delivery at the time of percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and thereby reducing the risk for post-myocardial infarction (ischemic) heart failure. Expected results and effects: The gradual implementation of new effective treatments against acute myocardial infarctions (AMI), including PCI, have not improved the survival after the myocardial infarction during the last decade. The reason is that this treatment does not affect the ischemia-reperfusion injury, which cause cell death and embolization of the micro-circulation. The CARMEV product holds the potential to inhibit these events and improve the recovery of myocardial function, thereby improving quality of life and cause reduction of hospitalizations. Approach and implementation: The project is divided into 3 Work Packages (WPs), with gradual development of immortalized cell-lines from the hpcMSCs in order to generate well defined EVs. The effectivity of these will be evaluated in in vitro immunomodulation and angiogenesis tests followed by in vivo evaluation in mouse infarction models. We will also study if cell-lines with constitutively active TNF-alpha receptors generate more effective EVs. The end product will be a well-defined EV-product, CARMEV, which next will be evaluated in large animal models.