Transplantation of parthenogenetic embryonic stem cells ameliorates cardiac dysfunction and remodelling after myocardial infarction.

ABSTRACT

AIMS: Parthenogenetic embryonic stem cells (pESCs) derived from artificially activated oocytes without fertilization presumably raise minimal ethical concerns and may serve as attractive candidates for regenerative medicine. Here we investigated whether pESCs could repair myocardial infarction (MI), in comparison to embryonic stem cells (ESCs). METHODS AND RESULTS: A total of 89 mice that survived coronary artery ligation randomly received an intramyocardial injection of undifferentiated pESCs, ESCs, or saline. Sham-operated mice (n = 21) that received no treatment served as control animals. After 7 days, transplantation of pESCs increased expression of pro-angiogenic factors and reduced leucocyte infiltration. By 14 and 30 days post-MI, similar to treatment with ESCs, treatment with pESCs efficiently prevented cardiac remodelling and enhanced angiogenesis, in contrast to saline-treated hearts. Improved heart contractile function was also notable 30 days following transplantation of pESCs. Immunofluorescence staining revealed that tissues regenerated from pESCs in the infarcted myocardium were positive for markers of cardiomyocytes, endothelial cells, and smooth muscle cells. Unlike ESC-treated mice, which exhibited a high incidence of teratoma (6 of 34), the pESC-treated mice showed no teratomas (0 of 30) 30 days following transplantation. CONCLUSION: Transplantation of pESCs could attenuate cardiac dysfunction and adverse ventricular remodelling post-MI, suggesting that pESCs may provide promising therapeutic sources for MI in females.