Extracellular vesicle production Microvesicles 100-1000nm
Exosomes 40-100nm
Extracellular vesicle subpopulation separation Organelles
Early endosome Secretion vesicles
Golgi Stress signals thrombin DNA damage intracellular calcium extracellular ATP LPS hypoxia
Apoptic bodies 1-5μm
Uptake pathways
Extracellular vesicle engineering
Reporter systems
A kick-start for the damaged heart Over 3.5 million people are diagnosed with heart failure in Europe every year, and their long-term prognosis is poor. Researchers in the Evicare project are developing an innovative therapy that could help to stimulate the repair of cardiac tissue and change the course of heart disease, as Professor Joost Sluijter explains. A number of
measures are commonly used to treat heart disease, such as lifestyle changes and certain medications like betablockers and ACE inhibitors, yet these typically only slow the progression of the disease. With heart failure the most common cause of death across the world, there is a clear need for effective new therapies, a topic at the heart of the Evicare project’s work. “We are looking into manipulating the response of the heart to injury, helping it to repair itself, so that we can essentially prevent heart failure,” outlines Professor Sluijter, the project’s Principal Investigator. This work centres on using stem-cell derived extracellular vesicles, containing nature’s own biological materials, to help repair the damaged organ. “One part of our research involves looking at the mechanisms of how this works. If you add the vesicles into the damaged organ, how does it help the repair mechanisms? Which cell types are targeted and which processes are affected?” explains Professor Sluijter.
Extracellular vesicles The aim here is to stimulate endogenous mechanisms in the heart using extracellular vesicles, which typically contain a mixture
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of proteins and different RNA species. These vesicles, which are derived from stem cells or made of synthetic materials, or a hybrid of the two, are being studied within the project on essentially three levels. “One part involves looking at the vesicle itself. We are looking to characterise the vesicles on the RNA and protein level, and we’re also investigating items like their density and size,” says Professor Sluijter. Researchers are also investigating the impact of these
A lot of attention within the project is focused on the question of how to deliver these extracellular vesicles to the location where they are required to help stimulate cardiac repair. These extracellular vesicles are so small that they could be moved away from the heart relatively easily, so Professor Sluijter says it’s important that they are delivered as accurately as possible to damaged parts of the organ. “We’re investigating how we can produce enough vesicles and how we can get them to the right location,” he says.
If you want to kick-start
a chronically ill heart and repair it effectively, then a single injection is unlikely to be enough. That’s why we think that local, slow-release systems are essential.
vesicles on certain cell culture systems. “We do in vitro studies where we put those vesicles on different cardiac cells in a culture model, and then we assess how they behave. The third level is where we go to in vivo studies – where we use pre-clinical animal models, mainly in rodents. There, we treat diseased hearts with the vesicles,” explains Professor Sluijter.
While it is possible to inject vesicles into the bloodstream, Professor Sluijter believes that a more localised approach is necessary in terms of the project’s wider objectives. “If you want to kick-start a chronically ill heart and repair it effectively, then a single injection is unlikely to be enough,” he continues. “That’s why we think that local, slow-release systems are essential. For a patient, it will mean a single operation.”
EU Research
