Abstract 19113: Cardiac Repair With Human-Induced Pluripotent Stem Cells-Derived Tri-Lineage Cardiac Cells in a Swine Myocardial Infarction Model
Introduction: Human induced pluripotent stem cells (hiPSC) derived cardiovascular cells hold great promise for cell-based therapy of heart diseases. However, efficiency of differentiation procedure and subsequent function of iPSC-derived cells may be influenced by epigenetic factors that iPSCs retain from their tissues of origin. Our previous results showed comparing to from dermal derived iPSCs, cardiomyocytes differentiated from human cardiac fibroblasts-generated iPSCs (hciPSCs) form a more mature, structurally aligned phenotype transplantation with high engraftment rate in a mouse model. To further test their clinical value, we utilized a swine myocardial infarct model to investigate functional impact and bioenergetic improvement of transplantation of tri-lineage cells derived from hciPSCs.
Methods: Female pigs were randomly assigned to four groups receiving: sham-operated group (n=7), MI only group (n=6), patch only group (n=7, MI injury plus a acellular fibrin patch), and cell+patch group (n=7, a fibrin patch containing 5 million hciPSC-cardiomyocytes, 2.5 million hciPSC-endothelial cells, and 2.5 million hciPSC-smooth muscle cells was put on the surface of ischemic myocardium; in addition, the same number and types of cells were injected into the injured myocardium). Cardiac function and infarction size were determined via magnetic resonance imaging. Myocardial bioenergetics was evaluated with a 31P MR spectroscopic system. Engraftment rate was assessed by histology.
Results: At 4 weeks post infarction, the cell+patch group showed significant better cardiac functional outcome than MI group or patch only group in terms of left ventricular ejection fraction and wall stress. The beneficial effects were also accompanied with alleviation of cardiac hypertrophy, reduction of scar size, and recovery of bioenergy metabolism. Histological analysis showed significant engraftment of hciPSC-derived cardiac cells up to 4 weeks post transplantation. The engrafted cells were functionally integrated onto host myocardium to generate organized sarcomeric structures and promote angiogenesis inside infarcted myocardium.
Conclusion: Our findings demonstrated the promising therapeutic potential of hciPSC-derived cardiac cells.
Author Disclosures: L. Gao: None. W. Zhu: None. J. Zhang: None.
- © 2016 by American Heart Association, Inc.