Abstract 1153: Adipose-derived Mesenchymal Stem-cell Therapy Improves Arteriogenesis, Hemodynamics, And Walking Performance In A Porcine Model Of Peripheral Artery Disease

Abstract

Background: There are few effective alternatives to revascularization for peripheral artery disease (PAD). We used our porcine model of PAD to test the hypothesis that adipose derived mesenchymal stem cells (ADMSC) injected around the aortic trifurcation in the pelvis improve ischemic limb hemodynamics and walking performance (WP). Methods: In Ossabaw miniswine (N=13, Age=6 mo) with metabolic syndrome, right (R) hindlimb ischemia was induced with R External Iliac and Superficial Femoral artery coil occlusion (T0) via carotid artery access. All swine had weekly testing of WP on a treadmill. At weeks 0 (T0), 4 (T4), and 8 (T8), ankle brachial indices (ABI) and muscle tissue oximetry (STO 2 ) were measured. At T4 and T8 all swine underwent angiography. At T4, in treatment (Tx) swine (N=4) ADMSC were isolated using stromal vascular fractionation of autologous abdominal wall fat. Using jugular vein access, a catheter with a retractable side-deploying needle was inserted in the R iliac vein and stabilized by a juxtaposed angioplasty balloon. The needle was deployed to access the retroperitoneum and ADMSC were infused around the aortic trifurcation. Results: Ischemic controls (IC) had no differences between T4 and T8 in ABIs, and mean STO 2 differences between R and L in calves and thighs. Tx improved both ABI and mean STO 2 measurements (table 1). IC had no changes in WP between T4 and T8, while Tx showed improvements (table1). On angiography, IC had growth of R Internal iliac artery (RIIA, the main inflow to the ischemic R hindlimb) and shorter appearance time (AT) of RIIA compared to L with no difference between T4 and T8. Tx showed increased growth of RIIA and shorter AT at T8 compared to T4 (table 1). Conclusion: In a clinically-relevant (similar to humans in size, anatomy, physiology and comorbidities) porcine model of PAD we found that ADMSC injection around the aortic trifurcation in the pelvis induces arteriogenesis and improves ischemic limb hemodynamics and walking performance.