Erythropoietin supports the growth and function of Sca-1+ stem cells and promotes myocardial infarction repair in mice

Background：Myocardial infarction (MI) is the leading cause of death in the world-wide population. With the improvement of clinical therapy, the mortality in acute MI cases has been significantly reduced. This study was to demonstrate that erythropoietin (EPO) is an effective supporter for Sca-1+ stem cells (SCs) and can promote the repair of myocardial infarction (MI) partially via way of enhancing Sca-1+ SCs activities. Methods: Darbepoetin alpha (a long-acting EPO analog, EPOanlg) (30 mg/kg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocytes apoptosis and regenerations and microvessels density were measured. Lin− Sca-1+ SCs were isolated from neonatal and adult mice hearts and were respectively used to identify the colony forming ability and the supporting effect of EPO on these Sca-1+ SCs. Results: Compared to MI alone, EPOanlg reduced the infarct percentage and cardiomyocyte apoptosis ratio and LV chamber dilatation, improved cardiac performance, increased the regenerated cardiomyocyte ratio in the border zone and the numbers of coronary microvessels, while without obvious adverse effects in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and Stat5-p38MAPK signaling. Conclusions: EPO promotes Sca-1+ SCs activities and MI repair. The study enlightens the prospects of Sca-1+ SC supporters in the treatment of MI.