Abstract 1281: Human Adipose Tissue-derived Stem Cells Potently Preserve Cardiac Function Resulting From Permanently Induced Myocardial Ischemia

Abstract

Background The use of stem cells has gained much interest as a potential therapeutic approach for repair of damage caused by a variety of cardiac insults. We and others have demonstrated the ability of pluripotent adipose-derived stem cells (ASCs), to promote repair in ischemic skeletal tissues. Here we demonstrate that ASCs also stimulate a robust functional improvement following acute myocardial infarction (MI) in rats. Methods and Results ASCs were harvested from human subcutaneous adipose tissue. ASCs were characterized in vitro before in vivo testing. Growth and metabolic activity of human microvascular endothelial cells (HMVEC) cultured in growth-factor deficient minimal medium (MM) increased 1.7-fold when supplemented with a 1:1 mixture of ASC CM ( p <0.01). Sprout formation by HMVECs and migration of endothelial progenitor cell (EPC) was enhanced by 2.1 and 2.0-fold, repectively, when ASC CM was added to MM ( p <0.01). Following demonstration of potency in vitro, the ASCs were evaluated for the ability to protect and rescue ischemic myocardium in an athymic nude rat following permanent ligation of the proximal LAD region. Immediately after ligation 10 6 ASCs in 100 μl saline or carrier alone was injected into 2 sites of the peri-infarct region, then at 4 and 28 d heart function was evaluated echocardiography using a Visualsonics Vivo770. ASC-treated rats consistently exhibited better cardiac function at 1 month compared to the saline control group. LV ejection fraction of the ASC group was 56 ± 7% (mean ± SEM) vs 37 ± 3% for the control (p<0.04). Fractional shortening was 32 ± 5% (ASC) vs 19 ± 2% (p<0.04). LV volumes both at end-diastolic and end-systolic stages were lower in ASC group (311 ± 17 μl and 139 ± 21 μl, respectively) than saline group (391 ± 30 μl and 249 ± 27 μl) (p<0.03). Anterior wall thinning was attenuated in ASC group (1.6 ± .08 mm vs 1.2 ± .2, at end-diastole, p<0.03). Post-mortem histological analysis demonstrated that ASC treated hearts had lower fibrosis (26 ± 6% vs 34 ± 6%; p<0.05). Conclusion We have demonstrated that ASCs have great potential as a cell therapy to preserve heart function following ischemic insult. Given the abundant source of ASCs, therapies with these cells have a higher potential for widespread adoption compared to more rare cell types.