Abstract 13163: Ultrastructural Features of Ischemic Tissue Following Application of a Bio-membrane Based Progenitor Cardiomyocyte Patch for Myocardial Infarction Repair
Background and Objective: Implantation of cell-sheets into damaged regions of the heart after myocardial infarction (MI) has been shown to improve heart function. We report here the potential role of applying a bio-membrane ‘cell patch’ created of cured fetal bovine serum and fetal mouse fibroblasts as a substrate for iPSC-derived precursor CM in a mouse MI model created by ligation of the left anterior descending (LAD) artery.
Methods and Results: iPSC derived progenitor cells were transduced using plv-IRES-ZsGreen (GFP)-firefly luciferase lentivirus vectors with a cardiac-specific Na+-Ca2+ exchange (NCX1) promoter in order to convey cardiogenic differentiation potential. iPSC-CM sheets were created on a substrate of cured albumin and fetal fibroblasts in thermo-responsive dishes and transplanted over the transmural myocardial infarction (MI) region in a mouse model. Mice were divided into four groups, 1) Sham; 2) MI; 3) MI + iPSC without NCX1 treated cells (MI+iPSCNull) and 4) MI + iPSC receiving NCX1 promoter treated cells (MI+iPSCNCX1). Echocardiography was performed 4 weeks after cell patch application, followed by histological and transmission electron microscopy (TEM) analysis (Fig. 1). More than 99% sarcomere alpha-actinin positive cells were obtained by group 4. Four weeks after cell patch application, large numbers of transplanted CMs were observed in the infarct region with significant improvements in left ventricular performance and remodeling in mice from group 4 as compared with group 3. No teratoma formation was detected in any of the treatment groups.
Conclusion: Manipulation of iPSC using viral vectors encoding markers under the control of NCX1 promoter yields large numbers of iPSC-CM with associated favorable morphological and ultrastructural tissue changes. These changes resulted in infarct size reduction and restoration of cardiac function after MI.
Author Disclosures: D. Chang: None. W. Cai: None. C. Paul: None. T. Okano: None. R. Millard: None. Y. Wang: None.
- © 2014 by American Heart Association, Inc.