Abstract 1119: Cardioprotective Effects of Wnt11-transfected BMSC Are Mediated by Over-expression of Various Cytokines
We hypothesized that over-expression of Wnt-11 in bone marrow stem cells (BMSCs) promotes cardiac repair and protect native cardiomyocytes via releasing various cytokines.
Methods: BMSCs were isolated from SD rats and transfected with WNT11 and GFP by retroviral expression system. Transfected BMSCs were transplanted into the border zone of infarcted myocardium and co-cultured with cardiomyocytes which were isolated from neonatal rat hearts in a ratio of 1 : 10. Myocardial function was analyzed by echocardiography and pressure-volume conductance system.
Results: The ejection fraction and fractional shortening respectively were significantly increased in WNT-11 BMSC treatment group (74.7 ± 1.4%; 36.5 ± 1.4%) compared to GFP-BMSCs group (59.9 ± 1.9%; 24.7 ± 1.2%) and medium control (48.7 ± 2.1%; 21.2 ± 0.5%). Hemodynamic parameters shown in Fig A~C⇓ indicated that heart function in the WNT11-BMSCs transplanted rats was significantly improved as compared with those transplanted with GFP-BMSCs and medium treated rats. WNT11-BMSCs also significantly protected native cardiomyocytes against hypoxia (24h) and H2O2 (200μmol, 2h) induced apoptosis (Fig. D⇓) and prevented DNA fragmentation. Moreover, WNT11-BMSCs significantly reduced LDH release induced by hypoxia for 36h compared to the GFP-BMSCs (Fig. E⇓). Microarray analysis or real-time PCR indicated that WNT11-BMSCs over-expressed various cytokines including VEGF (Fig. F~G⇓).
Conclusions: These data suggest that WNT11-BMSCs significantly improved heart functions by reducing cell injury through anti-apoptotic effects of various cytokines.