Does pretreatment of bone marrow mesenchymal stem cells with 5-azacytidine or double intravenous infusion improve their therapeutic potential for dilated cardiomyopathy?
Sirui Yang, Jinhua Piao, Lianhua Jin, Yan Zhou
Med Sci Monit Basic Res 2013; 19:20-31
Available online: 2013-01-14
Background: This study was designed to investigate whether pretreatment of bone marrow mesenchymal stem cells (BMSCs) with 5-azacytidine (5-aza) or double intravenous infusion could enhance their therapeutic potential for dilated cardiomyopathy (DCM).
Material/Methods: BMSCs were cultured for 2 weeks in the presence or absence of 5-aza and DCM serum. The cultured BMSCs (Groups 1 and 2), 5-aza-induced BMSCs (Groups 3 and 4), and medium alone (model control) were transplanted into 80 female Wistar rats by intravenous tail vein injection. Double infusion of BMSCs with 1-day time-interval was carried out in Groups 2 and 4. Postmortem histological analysis and evaluation of heart function were performed at 4 weeks post-transplantation.
Results: Some transplanted BMSCs engrafted into myocardial tissue and were positive for cardiac marker troponin T. The hearts containing transplanted BMSCs secreted a larger amount of vascular endothelial growth factor. Cardiac function parameters and serum level of brain natriuretic peptide (BNP) did not differ among Groups 1, 3, and the model control. As compared with model control, BMSC transplantation in Groups 2 and 4 significantly decreased the serum level of BNP and improved cardiac contractile function, as evidenced by reduced left ventricular end-diastolic and end-systolic diameter, elevated ejection fraction, and fractional shortening.
Conclusions: BMSC transplantation is a promising strategy for the treatment of DCM. Pretreatment of BMSCs with 5-aza and DCM serum does not enhance their therapeutic efficacy, and the double intravenous BMSC infusion method is superior to single infusion for preserving cardiac contractile function in a rat model of DCM.
Keywords: Myocardium - pathology, Natriuretic Peptide, Brain - blood, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells - metabolism, Infusions, Intravenous, Heart Function Tests, Gene Expression Regulation - drug effects, Fibrosis, Collagen - metabolism, Cell Transdifferentiation - drug effects, Cardiomyopathy, Dilated - therapy, Bromodeoxyuridine - metabolism, Bone Marrow Cells - metabolism, Body Weight - drug effects, Animals, Azacitidine - pharmacology, RNA, Messenger - metabolism, Rats, Rats, Wistar, Survival Analysis, Troponin T - metabolism, Vascular Endothelial Growth Factor A - metabolism