Abstract 18897: Genetically Purified Induced Pluripotent Stem Cell (IPSC)-derived Cardiomyocytes Engraft and Improve Remodeling and Ventricular Function After Myocardial Infarction in Mice
Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes in vitro and represent a possible autologous cell source for myocardial repair. The aim of this study was to determine the engraftment and functional effects of murine iPSC-derived cardiomyocytes (iPSC-CMs) in a mouse model of myocardial infarction. A genetic purification protocol was used to maximize CM yield and purity.
Methods: Murine iPSCs were genetically modified to express a Zeocin resistance gene under control of the cardiac-specific α-myosin heavy chain (α-MHC) promoter. Differentiation was initiated by hanging drop technique. Embryoid bodies were brought into suspension culture. CM selection was started on d7 (400 µg/ml Zeocin). 1x10^6 cell tracer (CFDA-SE) marked iPSC-CMs were transplanted into the hearts of LAD-ligated mice. Animals were treated with placebo (PBS, n = 14) or iPSC-CMs (n = 35). Heart function was evaluated by magnetic resonance imaging (MRI) and conductance catheter (CC) analysis. In vitro and in vivo differentiation was investigated. Follow up after iPSC-CM transplantation was 1 and 2.5 weeks (histological assessment only) or 4 weeks (including functional analysis).
Results: iPSC-CM purity was >90% after antibiotic resistance selection. Intramyocardial transplantation of iPSC-CMs significantly improved myocardial remodeling (e.g. infarct size and ventricular wall thickness, P<0.01) and left ventricular function 4 weeks after LAD-ligation (e.g. LV-EF, P<0.01). iPSC-CMs engrafted within ischemic myocardium, expressed cardiac markers and exhibited sarcomeric structures up to 2.5 weeks after transplantation. Connexin staining did not show functional coupling with host myocardium.
Conclusions: iPSCs can effectively be differentiated into cardiomyocytes with high purity by genetic engineering techniques. iPSC derived cardiomyocytes engraft within the myocardium of LAD-ligated mice and improve left ventricular function. Future research has to focus on long term survival and functional coupling to host myocardium.
- © 2012 by American Heart Association, Inc.