Transplantation of induced bone marrow mesenchymal stem cells improves the cardiac function of rabbits with dilated cardiomyopathy via upregulation of vascular endothelial growth factor and its receptors

Abstract

Bone marrow mesenchymal stem cells (BMMSCs) have shown promise in repairing injured myocardium. However, few studies have explored the potential of BMMSC transplantation for dilated cardiomyopathy (DCM). In this study we aimed to examine whether BMMSC transplantation improves the cardiac function of dilated cardiomyopathy and investigate the underlying mechanism. We established a DCM model in rabbit, then transplanted BMMSCs induced by 5-azacytidine into the rabbit, and determined the left ventricular pressure and the expression of vascular endothelial growth factor (VEGF) and its receptors. Immunohistochemistry, ultrastructural and reverse transcription polymerase chain reaction (RT-PCR) analysis proved that 5-azacytidine induced the differentiation of BMMSCs into cardiomyocyte-like cells. Upon transplantation of the induced BMMSCs into a DCM model, significantly higher maximum rates of rise and decline (±dp/dt) of left ventricular pressure and left ventricular systolic pressure, as well as much lower left ventricular diastolic pressure, were observed compared with the control group (P < 0.05). After four weeks, deposition of collagen fibers in the myocardium of transplantation group was reduced, accompanied by increased expression of VEGF and its receptors as detected by RT-PCR. Taken together, our results suggest that BMMSC transplantation could alleviate DCM through angiogenesis via the upregulation of VEGF and its receptors.

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

“…Accumulating data in the literature has demonstrated that transplanted BMSCs may improve cardiac function in the rat model of acute or chronic myocardial infarction (MI) [8–10]. Therefore, cell therapy with BMSCs has been attempted to attenuate LV remodeling and preserve cardiac function in the rat model of DCM [11,12]. More significantly, a randomized double-blind and placebo-controlled trial also demonstrated the safety and efficacy of autologous BMSCs transplantation in human patients with DCM [13].…”

α-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in regulating morphology of cardiomyocyte and tumor progression in tissue microenvironment

“…Clinical and experimental evidence suggests that the blood flow is the key of all the elements [1]. Abnormality of vascular net can contribute to retardation of development in embryo [2], cardiomyopathies in heart [3,4], progression and metastasis in malignancy [5], and so on.…”

Stem‐cell therapy for dilated cardiomyopathy: a pilot study evaluating retrograde coronary venous delivery

“…As a result of the ultimately poor prognosis even with standard medical management of DCM, interest has developed in regenerative treatments such as stem-cell therapy (Mu et al 2011). Cardiac cellular transplantation seeks to maintain or even improve left ventricular function with implantation of progenitor cells capable of decreasing fibrosis, increasing neovascularization, and less likely, producing new cardiomyocytes .…”

“…, Mu et al . ). Therefore, similar improvements may be found with naturally occurring DCM in Dobermanns, even in the occult stage of the disease.…”

“…Relatively less research on stem-cell therapy in models of non-ischaemic heart disease (such as DCM) has been performed. In such studies, improvement in systolic function, increased angiogenesis, and reduction in myocardial collagen deposition have, however, been observed (Nagaya et al 2005, Zhou et al 2010, Mu et al 2011. Therefore, similar ttp://www.bsava.com/ Journal of Small Animal Practice • Vol 54 • July 2013 • © 2013 British Small Animal Veterinary Association anti-arrhythmic therapy, if clinically indicated.…”