Progenitor Cells for Abdominal Aortic Aneurysm.
Ibrahim Aboshady, Deborah Vela, Kamal G Khalil, L Maximilian Buja. The Texas Heart Institute, Houston; The University of Texas HSC, Houston
Background: Current forms of treatment of abdominal aortic aneurysm (AAA) utilize open surgical repair or endovascular exclusion with a stent graft; both of which have major side effects with potentially life-threatening consequences. The aim of this study is to assess the potential role of progenitor cells in attenuating the progression, preventing rupture and providing treatment of aortic aneurysmal dilatation.
Design: AAA was induced in the infrarenal abdominal aorta of forty two 20-week old C57BL/6 Apo E -/- mice; maintained on a western diet beginning at week 4; by periarterial application of calcium chloride (0.5M). Angiotensin II was administered to dedicated groups of animals (500-1000ng/min) for 28 days via subcutaneous osmotic minipumps to enhance aneurysm growth. Stem cell antigen-1 positive, c-kit positive, Lin-negative progenitor cells; separated using immunomagnetic beads, were isolated from primary cultures of bone marrow of green-fluorescent-protein (GFP) C57BL/6 mice to facilitate tracking. Sorting of cells was done through fluorescent antibody cell sorting flow cytometry using FITC-conjugated rat anti-mouse Sca-1 antibody. Cells were injected intramurally at the site of maximum dilatation using sharpened capillary tubes to accommodate the diameter of the vessel wall.
Results: Measurements of the maximum cross-sectional diameter of the aneurysmal and normal segments of the aorta were done before and after each step; in situ (using a specialized calibrated digital camera), in vivo using state-of-the-art high-resolution micro-ultrasound imaging system (Vevo 770) designed especially for small animal imaging research and from histology (Visualsonics Inc., Toronto, Canada). Echocardiographic and digital measurements showed ∼ 11.5% reduction of the mean maximum cross-sectional diameter after application of progenitor cells to the aneurysmal segments of the suprarenal aorta (mean=0.93 +/- 0.28 vs. 1.04+/-0.24 mm) and ∼ 10.1% reduction (mean=0.69 +/- 0.12 vs.0.77 +/- 0.09 mm) in the aneurysmal segments of the infrarenal aorta compared to non-aneurysmal segments and controls. Histopathologic examinations of the ex vivo aortic sections showed non-significant differences in measurements among the aneurysmal and non-aneurysmal segments from test groups and controls.
Conclusions: This is a less invasive, fast and potentially effective stem cell therapy to help in delaying eventual rupture of AAA. Further studies are needed to further assess and maximize the capabilities and limitations of this novel technique.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 36, Wednesday Afternoon