Abstract 19423: Co-Transplantation of iPS Cell-Derived Cardiomyocytes and Mesenchymal Stem Cells for the Regeneration of Infarcted Myocardium
Introduction: In this study the regenerative potential of co-transplantation of cardiomyocytes derived from induced pluripotent stem cells (iPS-CM) and mesenchymal stem cells (MSC) was assessed in a mouse model of myocardial infarction.
Methods: After induction of myocardial infarction in CL57BL/6 mice, either iPS-CM expressing EGFP and luciferase, or magnetically labeled MSC, or a combination of both or saline were transplanted intramyocardially. Cell retention of iPS-CM by in vivo bioluminscent imaging (BLI), and magnetically labeled MSC by MRI was performed sequentially over four weeks. MRI was also used for the assessment of left ventricular ejection fraction (LVEF) at weekly intervals. Hearts explanted 1, 2 and 4 weeks after transplantation were analyzed histologically to locate and quantify transplanted cells, evaluate infarction size and structural integration of iPS-CM.
Results: Transplanted cells were tracked over the course of four weeks by BLI for iPS-CM showing a 80% decrease in luminiscence intensity and no loss of signal for MSC by MRI. LVEF increased significantly in the iPS-CM/MSC (55.7±2.3%) compared to MSC (47.6±1.9%; p<0.001) and sham (44.2±2.6%; p<0.001) groups at 4 weeks after transplantation. Infarct size was significantly decreased in iPS-CM/MSC (2.1±0.8 mm2) compared to MSC (5.0±1.9 mm2; p<0.02) and sham (8.4±3.4 mm2; p<0.01). Immunohistochemical analyses for α-actinin and connexin 43 revealed functional integration and structural maturation of iPS-CM.
Conclusion: The synergistic effects of co- transplanted iPS cell-derived cardiomyocytes and MSC resulted in functional integration and structural maturation of iPS-CM and, in turn, improved recovery of heart function after myocardial infarction. This novel approach opens a new perspective for the regenerative therapy of the heart.
- © 2012 by American Heart Association, Inc.