PT  - JOURNAL ARTICLE
AU  - Jonathan Leor
AU  - Sharon Gerecht
AU  - Smadar Cohen
AU  - Liron Miller
AU  - Radka Holbova
AU  - Anna Ziskind
AU  - Michal Shachar
AU  - Micha S Feinberg
AU  - Esther Guetta
AU  - Joseph Itskovitz-Eldor
TI  - Human embryonic stem cell transplantation to repair the infarcted myocardium
AID  - 10.1136/hrt.2006.093161
DP  - 2007 Oct 01
TA  - Heart
PG  - 1278--1284
VI  - 93
IP  - 10
4099  - http://heart.bmj.com/content/93/10/1278.short
4100  - http://heart.bmj.com/content/93/10/1278.full
SO  - Heart2007 Oct 01; 93
AB  - 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 (hESCMs) on cardiac function in a rat model of myocardial infarction (MI).Methods: Undifferentiated hESCs (0.5–1×106), human embryoid bodies (hEBs) (4–8 days; 0.5–1×106), 0.1 mm pieces of embryonic stem-derived beating myocardial tissue, and phosphate-buffered saline (control) were injected into the normal or infarcted myocardium of athymic nude rats (n = 58) by direct injection into the muscle or into preimplanted three-dimensional alginate scaffold. By 2–4 weeks after transplantation, heart sections were examined to detect the human cells and differentiation with fluorescent in situ hybridisation, using DNA probes specific for human sex chromosomes and HLA-DR or HLA-ABC immunostaining.Results: Microscopic examination showed transplanted human cells in the normal, and to a lesser extent in the infarcted myocardium (7/7 vs 2/6; 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 disorganised myofibres, 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, this study shows that hESC-derived cardiomyocyte transplantation can attenuate post-MI scar thinning and left ventricular dysfunction.