Abstract 10125: A Fibrin Patch-based Enhanced Delivery of Human Embryonic Stem Cell-derived Vascular Cell Transplantation Improves Cardiac Function in Postinfarction LV Remodeling
Background: It remains unclear concerning how to use human embryonic stem cells (hESC) to effectively treat hearts with postinfarction LV remodeling. In this study, we demonstrate that combined transplantation of hESC-derived endothelial (EC) and smooth muscle cells (SMC) via fibrin patch improves cardiac function in both rodent and porcine models with postinfarction LV remodeling.
Methods: hESC-derived EC and SMC were generated with stable expression of GFP and luciferase. Immunodeficient mice underwent LAD ligation followed by transplantation of saline (MI), 1×106 hESC-derived EC (MI+EC) or 5×105 each of hESC-derived EC and SMC (MI+EC+SMC). Young Yorkshire pigs were subject to myocardial infarction for 1 hr followed by reperfusion. Animals were subsequently randomized to receive no treatment (MI), empty fibrin patch (MI+P) or fibrin patch seeded with 2×106 each of hESC-derived ECs and SMCs (MI+P+C). Temporal changes of cardiac function were examined by echocardiography (mice) and MRI (pigs) up to 1 month. Transplanted cells were tracked by in vivo and ex vivo bioluminescent imaging (BLI) and vascular density was assessed by immunohistochemistry.
Results: Mice study: Although both MI+EC and MI+EC+SMC groups showed persistent cell engraftment as confirmed by BLI signal up to 8 weeks post-treatment, only MI+EC+SMC mice showed significant cardiac improvement compared to MI group (ejection fraction: 32±4%; vs. 15±3%;, p<0.05). Pig study: only MI+P+C pigs showed significant cardiac functional improvement compared to MI group in terms of ejection fraction (52±1%; vs. 44±3%;, p<0.05) and thickening fraction (infarct region: 2±3%; vs. −7±4%;, p<0.05). The beneficial effects were associated decreased scar size along time, reduced LV wall stress (MRI) and increased neovascularization (VWF staining) in both infarct and peri-infarct regions.
Conclusion: These findings demonstrate a promising therapeutic potential of using these hESC-derived vascular cells and the mode of fibrin patch delivery. The mechanism underlying the beneficial effects of cell transplantation is attributed to the increased neovascularization, improved myocardial energetics and possibly reduced native cardiomyocytes apoptosis secondary to paracrine effects.
- © 2010 by American Heart Association, Inc.