Abstract:
AIM To investigate the effects of nucleostemin (NS) on the survival and cardioprotective effects of adipose tissue-derived mesenchymal stromal cells (ADSC).
METHODS ADSC obtained from C57BL/6J mice were transfected with adenovirus harboring NS (ADSC-NS) or control (ADSC-Con). Mice were subjected to myocardial infarction (MI) or sham operations. Immediately after coronary artery occlusion, MI mice were intramyocardially injected with ADSC-NS (2 × 105 fresh ADSC-NS per mouse) or ADSC-Con (2 × 105 fresh ADSC-Con per mouse), both of which were stained with CM-DiI dye before transplantation. The survival of ADSC and cardiomyocyte apoptosis were determined 3 days after MI. Cardiac functions, fibrosis, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA expressions were evaluated 4 weeks after MI. In the in vitro studies, cultured ADSC were subjected to the following six groups: (1) ADSC-Con, (2) ADSC-NS, (3) ADSC-Con + Control, (4) ADSC-NS+Control, (5) ADSC-Con + H2O2, (6) ADSC-NS + H2O2. ADSC proliferation, migration and anti-apoptosis were investigated.
RESULTS Both immunostaining and flow cytometric analyses showed that ADSC-NS significantly increased (P < 0.05) ADSC survival in myocardial peri-infarcted area 3 days after injection as compared to ADSC-Con. In addition, ADSC-NS treatment significantly (P < 0.05) reduced cardiomyocyte apoptosis. Echocardiographic studies showed that ADSC-NS, not ADSC-Con, significantly improved the left ventricular ejection fraction (LVEF) 4 weeks after MI. ADSC-NS transplantation significantly mitigated MI-induced fibrosis. In vitro studies showed that NS over-expression significantly increased ADSC growth and reduced H2O2-induced ADSC apoptosis.
CONCLUSION NS over-expression increases ADSC survival and cardioprotection.