P-082 - THE HUNT FOR A MEDICAL TREATMENT OF ABDOMINAL AORTIC ANEURYSMS - ADIPOSE DERIVED STEM CELLS

TOPIC:
Vascular Biology
AUTHORS:
Kavaliunaite E. (Elite Research Centre of Individualised Treatment of Arterial Disease (CIMA), OUH ~ Odense ~ Denmark) , Lindholt J.S. (Elite Research Centre of Individualised Treatment of Arterial Disease (CIMA), OUH ~ Odense ~ Denmark) , Stubbe J. (Renal and Cardiovascular Research Unit, Institute for Molecular Medicine, SDU ~ Odense ~ Denmark)
Introduction:
The only treatment offered to AAA patients is open or endovascular surgical repair. Mesenchymal stem cells derived from adipose tissue (ASCs) have the unique ability to suppress immune responses and modulate inflammation - key players in the pathophysiology of AAA. We aimed to investigate whether ASCs treatment inhibits AAA progression in rats. We hypothesized that ASCs will attenuate AAA progression by reducing inflammation and enhancing remodeling.
Methods:
Based upon earlier studies, sample size calculation concluded 24 rats (12 in in each group) are needed to detect a 50% reduction in aneurysmal progression rate, which is considered clinically relevant. Preoperatively male Sprague-Dawley rats were randomly and blinded to the operator divided into 2 groups: (i) 0,1ml saline was intravenously injected through tail vein (controls), (ii) 0,1 ml containing 106 ASCs via tail vein. Adipose tissue was harvested from adipose tissue of all 24 rats and ASCs freshly isolated in half of them by staff in the neighboring Odense Stem Cell Centre, who also prepared the saline placebo injections. Then, AAA was induced in the same rats by intraluminal elastase injection (10 units/ml) and their isolated autologous ASCs were injected just after AAA induction in half, and saline in the other half by thus blinded surgeons. Primary outcome was change of aortic diameter. Blinded from treatment allocation, aortic diameter was measured by weekly ultrasound for 28 days with a LogiQe ultrasound machine and a L10-22-RS transducer, GE Healthcare, UK). Rats were sacrificed 28 days after the injection of ASCs. Harvested AAA were analyzed histologically for secondary outcomes. A two-way ANOVA test was used to evaluate diameter changes. histological changes were evaluated by Student's t-test. Statistical analyses were performed using SPSS (IBM SPSS Statistics, IBM Corporation, Endicott, NY, USA, 1989, 2020).
Results:
At the end of the 28 day experiment, ultrasound measures demonstrated mean aortic expansion of 179% (standard deviation (SD)= 80) in the control group and 207% (SD= 124) in ASCs group when compared with pre-operative aortic diameters, with no significant difference between groups (p>0.05). Comparative secondary histological analyses of aneurysm cross sections were performed blinded to treatment allocation. Myeloperoxidase (MPO) staining was used to evaluate neutrophilic infiltration. No difference was detected between groups; control group mean: 22.5 cells/mm2 (SD= 18.1) vs. 25.4 cells/mm2 (SD= 12.9) in the ASCs group, p>0.05. Also infiltrating macrophages (CD68 positive cells) were not affected by ACS treatment (0.02% (SD = 0.03)) of the aneurysm area in controls and (0.01% SD= 0.01) ASCs treated rats, p>0.05. Elastin degradation and disruption were also assessed, and no differences were exposed.
Conclusion:
Based on our results of this strictly blinded experiment , ACSs do not seem to protect against AAA progression. Though ACSs therapy in other regenerating area is very promising, our data does not support ACSs as an attractive intervention for patients with progressing AAAs. Further research is needed to assess potential therapeutic effect.