A. H. Hakim1, J. K. Salaymeh1, A. Al-Gahmi1, K. Brunette1, C. Shields1, Y. Tian1, J. Kim1, Z. Zhun1, G. Casale1, I. I. Pipinos1, M. A. Carlson1 1University Of Nebraska College Of Medicine, Surgery, Omaha, NE, USA
Introduction: Current approaches to stem cell-based therapies for peripheral arterial disease (PAD) usually involve injection of cells in muscles neighboring occluded arterial segments or infusion of cells in arteries with distal occlusive disease. Our group has taken the approach of delivering cells around proximal patent arteries to facilitate their growth as inflow collateral channels that can support distal ischemic arterial beds. We describe here our technique using a transvenous approach for para-arterial delivery of stem-cells.
Methods: Metabolic syndrome was induced in Ossabaw pigs (N = 5; 4 males; 6-8 months) using a high fat/fructose/sodium diet. Right hindlimb ischemia was then established via endovascular coil-occlusion of the right external iliac and right superficial femoral arteries. Four weeks later, adipose-derived stem cells were isolated using stromal vascular fractionation (SVF) of autologous fat obtained from the abdominal wall ~450 grams. An arterial reentry catheter (Outback®) and an angioplasty balloon were inserted into the left common iliac vein via internal jugular access. Balloon inflation opposed the catheter to the vein wall and the lateral-deploying needle was used to access the retroperitoneum, allowing for the infusion of cells around the iliac arteries. Contrast and methylene blue were used to confirm the infusion site with angiography and a laparotomy, respectively. Pre- and post-injection survivability of stem cells were assessed using hemocytometry (N = 4) to determine the effect of shear stress on the injected cells during their passage through the Outback® catheter.
Results: In all five cases, the retroperitoneum was accessed successfully with visualization both on angiography and laparotomy. Our proximal inflow arterial targets, the distal aorta, right and left internal iliac and left external iliac arteries were fully coated in methylene blue. There was no evidence of retroperitoneal bleeding at 2 hours post injection. Our SVF preparation yielded 53.45 ± 23.25 million cells. Pre-injection survivability was 90.8± 3.4%. Our post-injection survivability after cell passage through the Outback® catheter was 86.6±10.4%.
Conclusion: Using a porcine model of hindlimb ischemia, we present a novel, minimally invasive method for transvenous stem cell delivery into a location not easily accessible using current percutaneous or endovascular techniques. In this pilot preclinical study, this method was reliable, safe, and effective with respect to immediate, post-injection cell survival. We plan to explore the ability of this method of stem cell delivery to improve outcomes of cellular therapy for limb ischemia by focusing the therapeutic effect on the arterial inflow.
