Extracellular vesicles and vascularized organoid stroke models

Stroke is the second-leading cause of death worldwide and a leading cause of long-term disability. However, current acute stroke treatment is limited to thrombectomy and thrombolysis that both have a limited treatment window. Unfortunately, until now, no preclinical stroke treatments have been translated into routine clinical use. The lack of translational success can be due to limitations in the stroke models used in research as the blood brain barrier in rodents are quite different than the BBB found in humans.

We are working on developing advanced human cellular stroke models for testing novel stroke treatment. For this, vascularized cerebral organoids could prove to be the perfect model for preclinical stroke treatment as a natural next step following screening in more simple stroke models. We are currently working with plasma extracellular vesicles as a possible treatment of stroke, as we have seen that remote ischemic conditioning releases cytoprotective EVs in the plasma. Pursuing these findings, we will study the conditioned EVs in more complex cell culture systems and are in need of developing a stroke model based on vascularized human cerebral organoids. In this way, we will be able to study the ability of BBB crossing of the EVs in conditions mimicking acute stroke in terms of how far the intact EVs penetrate the tissue and the fate of EV content in the vasculature and possibly in astrocytes, glia and neurons. In addition, we will study the protective effects of the conditioned EVs in this complex system containing neurons, glia, and vascular components of the brain. In this way, we hope to bridge the translational gap in stroke research to facilitate the clinical implementation of neuroprotectants found in preclinical research for acute stroke treatment.

In addition to good collaborative skills, we are looking for expertise and skills in organoid models including experience in working with human IPSCs.

Knowledge of relevant microscopic techniques is an advantage as well as techniques in cell characterization and isolation.

We have a close collaboration with neurologists at the department of neurology at Aarhus University Hospital and have been working for years on stroke related projects within acute stroke diagnostics and treatment. As part of these projects we have implemented and optimized techniques within blood fractionation and diagnostics with a focus on extracellular vesicles (EVs) and miRNAs, cellular stroke models - currently mono culture models using the xCELLigence platform of real-time monitoring, and ways of manipulating cell and EV content.

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