Thorac Cardiovasc Surg 2012; 60 - PP26
DOI: 10.1055/s-0031-1297673

Induced pluripotent stem cell (iPSC)-derived cardiomyocytes engraft and improve heart function in a mouse model of acute myocardial infarction

A Martens 1, G Kensah 1, S Rojas 1, A Rotärmel 1, H Baraki 1, A Haverich 1, U Martin 1, I Gruh 1, I Kutschka 1
  • 1Medizinische Hochschule Hannover, Klinik für Herz-, Thorax-, Transplantations- und Gefäßchirurgie, Hannover, Germany

Aims: Induced pluripotent stem cells (iPSC) represent a suitable autologous cell source for myocardial regeneration and can be differentiated into cardiomyocytes in vitro. We evaluated the potential of murine iPSC-derived cardiomyocytes (iPSC-CM) to restore myocardial tissue and improve cardiac function after acute myocardial infarction in mice. In vitro purification protocols were devised to maximize CM yield and purity for transplantation.

Methods: Undifferentiated iPSCs were transfected with a plasmid driving the cardiomyocyte specific expression of an antibiotic resistance gene. Differentiation was initiated by hanging drop technique. Cells were brought into suspension culture on day 5. Cardiomyocyte selection was performed on day 14. 1×106 iPSC-CMs were transplanted into the ischaemic myocardium of left anterior descending coronary artery (LAD)-ligated mice. Infarcted animals were treated with placebo (phosphate-buffered saline, n=13) or iPSC-CMs (n=13). Heart function was evaluated by magnetic resonance imaging and conductance catheter analysis. Cardiogenic in vitro and in vivo differentiation was investigated by immunofluorescence staining. Follow up was one week. A second series with a follow up of four weeks is currently under investigation.

Results: iPSC-CM purity was >90% after antibiotic resistance selection. Intramyocardial transplantation of iPSC-CMs resulted in a favourable myocardial remodelling and improved left ventricular function after LAD-ligation. iPSC-CM engrafted readily within the ischemic myocardium. They expressed cardiac markers Troponin T and Titin and formed gab junctions as shown by Connexin staining.

Conclusions: iPSCs can effectively be differentiated into cardiomyocytes with high purity by genetic engineering techniques. iPSC derived cardiomyocytes engraft within the ischemic myocardium of LAD-ligated mice and improve left ventricular function.