Abstract 19008: Biodegradable Multilayered Aligned Nanofiber Cardiac Patch Composed of Human Inducible Pluripotent Stem Cell Derived Cardiomyocytes (hiPSC-CMs) Enhances Cardiac Function and Cell Survival In Vivo
Introduction: The current obstacles to regenerate ischemic cardiac tissue using the stem-cell based therapies include poor survival of transplanted cells in the ischemic heart, lack of anisotropic structure for alignment of cardiomyocytes and thickness of the engineered cardiac tissue.
Hypothesis: We hypothesized that a biodegradable multi-layered hiPSC-CMs aligned nanofiber (PLGA) cardiac patch mimics the anisotropic structure and alignment of transplanted cardiomyocytes, thereby improves cell survival and cardiac function following transplantation onto the ischemic myocardium.
Methods: Study was divided into four different groups as follows: 1) Control (no-MI); 2) MI (Permanent LAD ligation); 3) S-CP (Single layer cardiac patch +MI); 4) M-CP (Multilayer cardiac patch+MI). Nude athymic rats (NIHRNU) were used for transplantation of human cardiomyocytes (rFP fluorescence). HiPSC-CMs were cultured for one-week on the aligned nanofiber scaffold. For multilayered patch, three single layers of cardiac patch were stacked together before transplantation onto the ischemic heart. Briefly, 30-min following permanent LAD ligation cardiac patch was sutured onto the epicardial heart surface. Cells were labeled with red fluorescent protein (rFP) and Quantom dots for cell tracking via fluorescence and MRI imaging. One-week following MI, non-invasive measurement of cardiac function (Echocardiography) and magnetic resonance imaging (MRI) was performed. Immunohistological studies were performed for assessment of cell engraftment and cardiac fibrosis.
Results: Significant improvement in percent ejection fraction was observed at one-week following MI in hearts transplanted with M-CP (66±4.2, p<0.05), when compared to a S-CP (49±4.0) or MI (41±3.0) groups. Furthermore, decreased cardiac fibrosis and increased rFP cell-engraftment was observed in M-CP group. Magnetic resonance imaging indicated localization of Quantom-dots labeled cardiomyocytes in the ischemic myocardium.
Conclusions: Overall, our results demonstrated that biodegradable multi-layered aligned nanofiber cardiac patch provides trophic support to the ischemic heart by enhancement of cell survival and cardiac function after MI.
Author Disclosures: M. Khan: None. J. Johnson: None. M.G. Angelos: None.
- © 2016 by American Heart Association, Inc.