Abstract 10828: Stem-Cell Therapy for Abdominal Aortic Aneurysms in Swine
Circulation(2021)
Abstract
Introduction: The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop drug or cell-based therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. A previously validated acute AAA swine model was treated directly with gelfoam containing human adipose-derived stem cells (h-ADSCs). Methods: Male Yorkshire swine (n=16) received periadventitial injections (type 1 collagenase and porcine pancreatic elastase) into a 4 cm segment of infrarenal aorta. Experimental group (n=7) received gel foam soaked with 10 million h-ADSCs and control group (n=9) media-soaked gel foam. Aortic diameters (AD) were monitored at post-operative day (POD) 7 and 14 using ultrasound with euthanasia on POD 21. Suprarenal (control) and infrarenal aortas (experimental) were harvested for PCR, mechanical tensiometry testing, histopathological analyses as well as immunohistochemistry (IHC). Each animal served as their own control. Groups were compared with paired t-tests and Mann Whitney U tests. Results: Twelve animals survived until POD 21. Stem cell treated AAAs, unlike controls, demonstrated no growth (-1.6 ± 8.8% vs. 34.8 ± 13.7%, p<0.001), and had greater medial thickness (682.7 ± 149.1 um vs. 321.7 ± 194.0 um, p<0.001), and greater areas of elastin (5.33 ± 1.49% vs. 2.57 ± 2.25%, p<0.0001), smooth muscle (55.8 ±6.59% vs. 24.0 ± 6.84%, p<0.001), collagen 1 (p=.014), and VEGF (p=.009) than untreated controls. MMP9 mRNA expression in stem cell AAA specimens was downregulated 0.501 (±0.464) fold compared to control segments from those same animals (p= 0.025). Though tensiometry data displayed greater strength within the stem cell AAA rings, this did not reach statistical significance (p=.15). Conclusion: Stem cell therapy prevents the development of aortic aneurysms in a swine model. Stem cell treated swine with induced AAAs show more normal gross features, histologic, and biochemical properties compared to untreated controls with induced AAAs. Further investigation is merited as a possible translatable therapy for aneurysmal disease.
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Key words
abdominal aortic aneurysms,swine,stem-cell
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