Abstract 4936: Endovascular Perfusion of Pluripotent Mesenchymal Stem Cells Stabilizes Already-formed Aortic Aneurysms in a Rat Model
Introduction: Endovascular cell therapy using catheter-based delivery of Vascular Smooth Muscle Cells (VSMCs) has been shown to stabilize diameter of expanding Abdominal Aortic Aneurysms (AAAs) in rat. Mesenchymal Stem Cells (MSCs) are able to differentiate into VSMCs after stimulation by Platelet Derived Growth Factor-BB (PDGF-BB). Our goal was to assess the impact of MSCs endovascular perfusion with or without pre-differentiation by PDGF-BB stimulation on aneurysm growth.
Materials and methods: After selection by plastic adhesion, bone marrow derived-MSCs were stimulated or not by PDGF-BB and phenotyped by immunohistochemistry. AAAs obtained by xenograft degeneration were perfused endovascularly with 1 million of VSMCs (n=5), MSCs (n=6), PDGF-MSCs (n=6) and medium culture as controls (n=4). Rats were euthanized 1 week later or 4 weeks later (non differentiated MSCs (n=6) and culture medium (n=5)) for diameter measurement and AAA harvesting for mRNA (MMP-9, TIMP-1) quantification.
Results: MSCs were CD90+, CD44+, CD45− and CD11b− and after PDGF stimulation strongly expressed calponin, α-actine and myosin. At 1 week, MSC infusion decreased aneurysm growth compared to SMCs and control group (% diameter increase: 6.5%+/−9.7, 25.5%+/−17.2 and 53.4%+/−14.4 respectively; p<0,05) whereas PDGF-MSCs increased aortic growth rate (55.6%+/−26.6; p<0,05) and induced rupture (n=3/6 AAAs). Perfusion of MSC decreased expression of MMP-9 and increased TIMP1 expression compared to controls. At 4 weeks, MSC signicantly decreased aneurysm growth compared to control group (9.2%+/−13.8 and 76.2%+/−17.4, respectively; p<0.05)
Conclusion: Pluripotent MSCs stabilized growth of expanding AAAs more efficiently than VSMCs and decreased proteolytic activity in the aortic wall. Predifferentiation suppressed the stabilization properties of MSCs, suggesting the importance of pluripotency of progenitors in aneurysm repair.