Abstract 11180: Fibrin Patch-Based Transplantation of Cardiovascular Progenitor Cells Enhanced the Repair of the Infarcted Myocardium
Background: The optimal cell delivery method for stem cell-based cardiac repair remains to be explored. In this study, we aim to enhance the efficacy of cardiac repair by using a fibrin patch-based transplantation of cardiovascular progenitor cells (CVPCs).
Methods and Results: CVPCs were derived from human embryonic stem cells and consisted of both endothelial and smooth muscle cells types. In vitro co-culture with cardiac muscle cell line HL-1 demonstrated anti-apoptotic capabilities of CVPC. CVPCs were transplanted to infarcted mice hearts using either intramyocardial injection or fibrin patch (n=8, each). The fibrin patch-based delivery demonstrated significantly better cell engraftment rate up to 2 weeks post transplantation (in vivo bioluminescent imaging), which was also accompanied by a better cardiac ejection fraction (p<0.05). Compared to ligation only mice, the CVPC-patch hearts demonstrated a significant reduction of apoptosis level (A & B). In addition, CVPC-patch transplantation induced extensive neo-vascularization (E), recruited significantly more endogenous c-kit+ progenitor cells (C), stimulated cardiac cell cycling (D), and prevented scar formation at nearby myocardium (F). CVPC patch was further applied to a swine model of ischemia/reperfusion. Pigs with 60 min distal LAD occlusion followed by reperfusion, were randomized to receive saline (MI), fibrin vehicle (MI+P) or CVPC-fibrin transplantation (MI+P+C, n=6 each). Cardiac function and myocardial perfusion were measured using MRI at 1 month. MI+P+C pigs demonstrated a significant better cardiac function (p<0.05). CVPC-fibrin transplantation also significantly ameliorated the impaired myocardial perfusion at both infarct and peri-infarct zones, which is attributed to the angiogenesis effects.
Conclusion: These findings demonstrate a promising therapeutic potential of using these cardiovascular progenitor cells and the mode of fibrin patch-based delivery.
- © 2011 by American Heart Association, Inc.