Human embryonic stem cell transplantation to repair the infarcted myocardium

Jonathan Leor ^1*, Sharon Gerecht-Nir ², Smadar Cohen ³, Liron Miller ¹, Radka Holbova ¹, Anna Ziskind ², Michal Shachar ³, Micha S Feinberg ⁴, Esther Guetta ¹ and Joseph Itskovitz-Eldor ²

¹ Tel Aviv University, Israel
² Technion, Israel
³ Ben-Gurion University, Israel
⁴ Tel-Aviv University, Israel

^* To whom correspondence should be addressed. E-mail: leorj{at}post.tau.ac.il.

Accepted 21 November 2006

Abstract

Objective: To test the hypothesis that human embryonic stem cells (hESCs) can be guided to form new myocardium by transplantation into the normal or infarcted heart, and to assess the influence of hESC-derived cardiomyocytes (hESCM) on cardiac function in rat model of myocardial infarction (MI).

Methods: Undifferentiated hESCs (0.5-1x10e6), human embroid bodies (hEBs) (4-8 days; 0.5-1x10e6), 0.1 mm pieces of ES-derived beating myocardial tissue, and phosphate buffer saline (PBS, control) were injected into the normal or infarcted myocardium of athymic nude rats (n=58) by direct injection into the muscle or into pre-implanted 3-D alginate scaffold. By 2-4 weeks after transplantation, heart sections were examined to detect the human cells and differentiation with fluorescent in situ hybridization (FISH), using DNA probes specific for human sex chromosomes and HLA-DR or HLA-ABC immunostaining.

Results: Microscope examination revealed transplanted human cells in the normal, and to a lesser extent in the infarcted myocardium (p<0.05). The transplanted hESCs and hEBs rarely created new vessels and did not form new myocardium. Transplantation of hESCM tissue into normal heart produced islands of disorganized myofibers, fibrosis and in a single case a teratoma. However, transplantation of hESCMs into the infarcted myocardium did prevent post MI dysfunction and scar thinning.

Conclusions: Undifferentiated hESCs and hEBs are not directed to form new myocardium after transplantation into normal or infarcted heart and may create teratoma. Nevertheless, the present study shows that hESC-derived cardiomyocyte transplantation can attenuate post MI scar thinning and left ventricular dysfunction.

Keywords: heart, heart failure, myocardial infarction, regeneration, stem cells

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