Nucleostemin enhances therapeutic efficacy of mesenchymal stromal cells in treatment of acute myocardial infarction

  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.