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Egle Kavaliunaite

Department of Thoracic, Cardiac and Vascular Surgery

The Hunt for a Medical Treatment of Abdominal Aortic Aneurysms -adipose derived stem cells

Abdominal aortic aneurysm (AAA) is a dilatation of the abdominal part of the aorta, and is a common disease in especially older men with a pathological dilatation causing the aorta wall to dilate. AAAs are mainly asymptomatic and be continuously growing until the event of rupture of the aorta wall, if death doesn´t occur of other reasons. AAA rupture is a life- threating event that always requires emergency surgical treatment.

Mortality of a ruptured AAA is over 80% The management of AAA is guided mainly by aneurysm size and sometimes by the rate of aortic diameter growth within periodic surveillance imaging. Small AAAs (However, as there currently is no medical treatment, this surveillance does not influence further enlargement and most small AAAs continue to enlarge after diagnosis and half undergo surgical repair later. Preventive surgical intervention is recommended for large AAA (>55 mm). These surgical interventions carry their own risks and complications, sometimes requiring additional interventions. Other patients might not be fit for surgery due to additional comorbidities.

While the etiology of AAA formation and growth is unclear at this time, we do know that an intense local inflammatory process leads to the loss of vessel wall integrity. For the last decades, tissue engineering and regenerative medicine showed promising potential therapeutic effects for various cardiovascular diseases, including AAA. The therapeutic benefit of mesenchymal stem cells (MSCs) in pathologies with substantial inflammatory responses such as chronic obstructive pulmonary disease, myocardial remodeling after infarction and others is noted. Several studies have described positive results of stem cell treatment in animal models of AAA, but none have translated these results in human trials yet.

This PhD project aims to investigate cell-based strategy for AAA by proposing stem cells as a treatment option. This study could potentially have a profound impact in the treatment of AAA. The ability to control AAA progression would be of tremendous importance to all the patients especially ones that are not fit for surgery. This would also provide patients will small aneurysms a treatment option that would minimalize the risk of AAA growth in size and thus the need for later surgical treatment. This need will expand as national screening programs are being implemented (latest in Germany, and expected in Denmark in 2021), which would increase the numbers under surveillance substantially. Furthermore, this project would benefit the understanding of the biological mechanism causing this disease. We hope the OUH PhD fund will acknowledge and help us conduct this project.

Methods

This study will comprise of two phases. First phase is going to be an Experimental study in a chronic rat AAA model. Second phase will be Human phase 1 clinical trial.

1) First phase will comprise of 48 rats divided in four groups of 12 rats in each (including a control group). Different stem cells and routes of applying stem cells will be used in each group. Progression of the rodents’ AAA will be followed by ultrasound and tissue samples will be collected and compared with the control group.

2) Second phase of the PhD protocol will be a non-randomised clinical trial based upon the experimental results from animal study. 20 male patients diagnosed in the DANCAVAS trial undergoing surveillance at Odense University Hospital or Kolding Hospital with 35-54 mm diameter large AAA will be enrolled. Their growth rate after stem cell application will be compared with 200 men with similar sized AAA from the DANCAVAS trial adjusted for factors influencing growth rate. For this part of the project, patients will be involved in designing the method of harvesting stem cells, enrolment and patient related outcomes.

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