The Study Of Parthenogenetic Embryonic Stem Cells Transplantation For Muirne Myocardial Infarction Therapy

Myocardial infarction (MI), one kind of the most serious symptoms of coronaryheart disease, is one of the leading causes of morbidity and mortality in the world.The clinical treatments for MI can greatly reduce the mortality, however, theprognosis is not ideal since the necrosis of large amount of cardiomyocytes due toischemic damage can not be reversed. Recent advances in stem cell biology havebrought about considerable hopes for the development of novel therapeutic strategiessuch as stem cell transplantation, which has been considered as one promising andeffective approach. A great deal of animal experiments showed that stem celladministration could effectively reduce the infarct size, restrain the cardiacremodeling and improve the heart function.Embryonic stem cells (ESCs) are a promising source of cardiomyocytes for cardiactherapy owing to their germline competency. Transplantation of ESCs can regeneratecardiomyocytes and repair the damaged myocardium, while, the risk of teratomaformation bothers its application. Parthenogenetic embryonic stem cells (pESCs) canprovide an alternative source for ESCs with strong differentiation capacity and mayserve as attractive candidates for regenerative medicine and stem cell therapy. pESCsare derived from artificially activated oocytes without fertilization and therefore raiseminimal ethical concerns and reduce cell immunogenicity. Since there have been noreports about the use of pESCs in MI treatment, we thought to investigate theircardiac repair capacity and focused on the differentiation, the effect on cardiacremodeling and heart function and the safety issue by intramyocardial-deliveredpESCs into acute MI-modeling mice.In the current study, we tested the cardiac repair effects and the safety issue ofpESCs transplantation on mouse MI model by direct comparison with those of ESCs.Mice (n=89) survived coronary ligation randomly received undifferentiated pESCs,ESCs, or saline. Sham-operated mice received no treatment (n=21). Animals weresacrificed in batches7,14,30and90days post MI on basis of different study purposes. After7days, pESCs transplantation promoted pro-angiogenic factorssecretion and reduced infiltrated leukocytes. Tissues regenerated from the engraftedpESCs in the infarcted myocardium were positive for cardiomyocyte, endothelial celland smooth muscle cell markers, indicating their cardiac and vascular differentiationin longer term studies. pESCs-treated hearts, superior to ESC group, showedprevented cardiac remodeling and enhanced angiogenesis in14and30days post MI.Heart contractile function was notably improved by administration of pESCs by30days and such benefits could be maintained three months. Furthermore, teratomafomation appeared in ESCs-treated mice in high proportion (6/34), but surprisinglynot found in pESCs-treated mice (0/30) by30days. Two intramyocardial teratomas,while, appeared in pESCs-grafted group in90days, which suggest the transplantationof pESCs was not absoultly safe.In conclusion, cardiac dysfunction and adverse ventricular remodeling post MIwere attenuated by pESCs transplantation, which may represent an effective andrelatively safer strategy for autologous cell therapy in females.