Abstract 14112: 3D Grafts Enriched with Subamnion Mesenchymal Stem Cell Angiogenic Spheroids Induce Post-Ischemic Myocardial Revascularization, Reduce Fibrosis and Recover Cardiac function in Rat Failing Hearts
Delivery of adult stem cells within cardiac patches results in limited donor cell survival. 3D cell aggregates may enhance cell-to-cell interactions and viability. A promising cell type from the subamnion, namely cord-lining mesenchymal stem cells (CL-MSC), was used to generate angiogenic spheroids. We assessed the hypothesis that epicardial delivery of subamnion-MSC angiogenic spheroids embedded within 3D fibrin grafts (SASG) improves donor cell survival, and enhances cardiac function in failing rat hearts. Self-assembly in hanging drops was used to produce angiogenic spheroids made of 1.5×104 human CL-MSC-GFP-Fluc coated with 2×103 HUVECS. SASG were constructed by embedding 150 spheroids in fibrin matrix. Myocardial infarction was induced in nude rats and echocardiography was carried out at baseline, and at 2 and 6 weeks after ischemia. Grafts were implanted 2 weeks after injury, upon confirmation of ensued heart failure. Except for untreated rats (MI, n=8), grafts were delivered through thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or by video-assisted thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). Cell survival was comparable between SASG groups throughout the study, with a non-significant decline in cell viability during the first week in vivo. After 4 weeks of treatment, left ventricular end-diastolic pressure was lower in SASG and SASG-VATS than MI (2.6±0.3 and 3.2±0.3, vs. 5.7±0.6mmHg), whereas fractional shortening was higher in SASG groups compared to MI (24.5±1.2, and 23.2±1.2, vs. 15.6±1.1%; P<0.0001 and P<0.01), and to FG groups (P<0.01 and P<0.05). A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG and SASG-VATS, while MI had a -11.4% drop in ejection fraction. Cardiac output was significantly higher in SASG groups relative to MI. Donor GFP+ cells were detected within the graft and infarct areas. SASG and SASG-VATS had smaller scar size (23±4.4 29±3.2%) than MI (56±3.9%; P<0.0001 and P<0.001), and had a higher amount of functional blood vessels compared to untreated hearts (P<0.01 and P<0.05). In conclusion, SASG treatment has the potential to repair failing hearts by enhancing cardiac function and myocardial revascularization, while attenuating cardiac fibrosis.
- © 2012 by American Heart Association, Inc.