[Effects of bone marrow mesenchymal stem cells transplantation on heart function and ventricular remodeling in rats with isoproterenol-induced congestive heart failure]

Abstract

Objective: To explore the effects of transplanted BMSCs (bone marrow mesenchymal stem cells) on cardiac function and ventricular remodeling in rats with isoproterenol (ISO) induced heart failure.

Methods: Wistar rats (n=50) received ISO (170 mg x kg(-1) x d(-1) for 4 days) injection. Four weeks later, rats with left ventricular ejection fraction (LVEF < 70%, n=26) were randomly assigned to receive intramyocardially BMSCs (2 x 10(7)/ml, 150 microl) injection (n=13) or equal volume culture medium (n=13). Another 10 normal rats served as normal controls. Four weeks after transplantation, heart function was assessed again by echocardiography, left ventricular morphology was evaluated through H&E and Masson's trichome staining. Transplanted cells were observed by fluorescent microscope. RT-PCR and Western blot were performed to examine the myocardial expressions of type I and type III collagens, as well as MMP-2 and MMP-9.

Results: LVEF [(78.51 +/- 6. 78)% vs. (65.40 +/- 12. 33)%] and LVFS [fractional shortening, (42.09 +/- 6. 53)% vs. (32.38 +/- 10. 22)%, all P < 0. 05] were significantly increased and LVDs [left ventricular systolic diameter, (2.91 +/- 0. 54) mm vs. (3.83 +/- 0.69) mm, P < 0.05] was significant decreased in BMSCs treated rats compared with culture medium treated rats. Myocardial fibrosis was also significantly attenuated in BMSCs rats than that in culture medium treated rats. The myocardial expressions of type I and type III collagens, as well as MMP-2 and MMP-9 were significantly decreased in the BMSCs group compared with those in culture medium treated group.

Conclusions: BMSCs transplantation can significantly improve heart function and attenuate LV remodeling in rats with ISO-induced heart failure mediated by reducing myocardial fibrosis and downregulation of myocardial MMP-2 and MMP-9 expressions.