Background: Cardiovascular disease is the leading cause of death in developed and developing countries. The lack of effective regenerative therapies in the treatment of ischemia‐related diseases requires new therapies to improve clinical outcomes. Thus, MSCs have become a focus in stem cell treatment of myocardial injury. At present, most studies use mixed MSCs in vivo and in vitro. A promising therapeutic strategy for myocardial injury should be using the dominant subgroup with essential biological characteristics. The aim of this study was to utilize the dominant CD73 + subgroup of adipose derived mesenchymal stem cells (ADMSCs) for the therapy of myocardial infarction (MI).
Methods: Adult mix gender SD rats, with a body weight of 230±18g, were randomly divided into sham operation group (SHAM), MI group (MI), mixed ADMSCs transplantation group (MI+ADMSCs), CD73 + ADMSCs transplantation group (MI+CD73 + ADMSCs) and CD73 - ADMSCs transplantation group (MI+CD73 - ADMSCs). CD73 + ADMSCs were isolated using flow cytometry and then cultured. Overexpression and inhibition of CD73 gene of ADMSCs using lentiviral vectors. Differential genes analysis of CD73 + ADMSCs vs. CD73 - ADMSCs were based on GO analysis. The effect of CD73 on the secretion of cytokines was measured by ELISA. Myocardial infarction model and cell transplantation model were replicated. Detection of cardiac function of rats by color doppler ultrasound after operation. The expression of VEGF and factor VIII and neovascularization were detected by immunohistochemistry and Western Blotting.
Results: We demonstrated that, compared to mixed ADMSCs and CD73 - ADMSCs, CD73 + ADMSCs were more effective in the promotion function of cardiac recovery in a rat model of MI. CD73 + subset promoted vascular regeneration in myocardial injured regions. We also showed that expression of CD73 promoted secretion of VEGF, HIF-1α and HGF factors in ADMSCs. CD73 + ADMSCs displayed significantly different transcription profile compared to CD73 - ADMSCs, in particular, concerning VEGF pathways.
Conclusions: Overall, CD73 + ADMSCs were the dominant subgroup and the presence of the surface marker CD73 can be used as a MSCs cell quality control for treatment of myocardial injury by angiogenesis.