Does pretreatment of bone marrow mesenchymal stem cells with 5-azacytidine or double intravenous infusion improve their therapeutic potential for dilated cardiomyopathy?

Abstract

BackgroundThis 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/MethodsBMSCs 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.ResultsSome 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.ConclusionsBMSC 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.

Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Alleviate Methotrexate-Induced Pulmonary Fibrosis in Rat: Comparison with Dexamethasone

“…Bone marrow mesenchymal stem cells (BM‐MSCs) are stem cells residing within the bone marrow microenvironment. BM‐MSCs possess the following advantageous features: convenient collection, rapid proliferation, expansion in vitro, persistent self‐renewal capacities in vivo, and lack of questionable ethical issues . During the past few years, several studies have demonstrated that BM‐MSCs can localize to and/or participate in the development of new lung tissue .…”

Comparison of hIGF-1 Gene Transfection to the hBMSCs and Human Meniscal Fibrochondrocytes

“…Effective gene expression and the resulting responses of the transfected cells are key factors for therapeutic outcomes of the procedure. Determining which cell type is more appropriate for application is critical, and factors such as differentiation potential, bone marrow mesenchymal stem cells, or differentiated cells like fibrochondrocytes should be considered [ 11 , 12 ].…”

Efficacy and Safety of Bone Marrow Cell Transplantation for Chronic Ischemic Heart Disease: A Meta-Analysis

“…The role of BMCs in impaired heart tissue could be multifunctional and multifactorial. Previous studies found that BMCs and bone marrow progenitor cells could secrete a series of cytokines that activate endogenous cardiac repair, such as activating resident cardiac progenitor cells and stimulating cardiomyocyte cell-cycle re-entry [ 37 , 38 ]. In addition, BMCs were involved in the process of neovascularization, inhibiting apoptosis of myocardial cells, and reducing inflammation through paracrine production of cytokines and growth factors [ 36 , 39 , 40 ].…”