Abstract 12878: In vivo Integration of Indueced Pluripotent Stem Cell-derived Bioartificial Cardiac Tissue
Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising source of cells for regenerating myocardium. We evaluated the histological, functional and electromechanical characteristics of bioartificial cardiac tissue (BCT) made from iPSC-CMs and embryonic stem-cell derived cardiomyocytes (ESC-CMs) implanted into infarcted rat hearts.
Methods and Results: BCT was prepared from a mixture of liquid collagen type I and Matrigel combined with mouse iPSC-CMs and γ-irradiated mouse fetal fibroblasts (10% of iPSC-CMs). They were conditioned in a bioreactor for 21 days, and implanted into the myocardium of nude rats with chronic myocardial infarction (n=15). Heart function was compared to control animals without BCT (sham, n=15) using echocardiography and magnetic resonance imaging. At 4 weeks, heart function was significantly better preserved in the BCT-group compared to the sham-group (left ventricular ejection fraction; 54±11% vs. 40±18%, p= 0.004; left ventricular end-systolic volume; 0.23±0.01mL vs. 0.45±0.01mL, p=0.001). Histological examination 4 weeks after the implantation revealed abundant survival of cardiomyocytes (α-Actinin). Gap-junction protein expression (connexin 40, 43, and 45) and neo-vascularization (CD31) were observed within the BCTs and at the borderzone to host myocardium. To evaluate the electrical coupling with the host myocardium, BCTs made from channelrhodopsin-2 transgenic mouse ESC-CMs were implanted into the myocardium of nude-rats (n = 6). Stimulation of the whole hearts with the blue light (475 nm) 4 weeks after the implantation induced a stimulation rate dependent ventricular arrhythmia of the host heart, suggesting relevant electromechanical coupling. No arrhythmia was induced in control rats without BCT (n = 3) by the blue light.
Conclusions: Bioartificial cardiac tissue made from mouse iPSC-CM/ESC-CM engrafts and survives in ischemic nude rat myocardium. Beneficial effects on left heart function may be explained by significant neovascularization and electromechanical connection between the tissue graft and host cardiomyocytes.
- © 2013 by American Heart Association, Inc.