Beneficial effects of intramyocardial mesenchymal stem cells and VEGF₁₆₅ plasmid injection in rats with furazolidone induced dilated cardiomyopathy

Abstract

To explore the impact of myocardial injection of mesenchymal stem cells (MSCs) and specific recombinant human VEGF165 (hVEGF165) plasmid on collagen remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM was induced by furazolidone (0.3 mg/bodyweight (g)/day per gavage for 8 weeks). Rats were then divided into four groups: (i) PBS group (n = 18): rats received equal volume myocardial PBS injection; (ii) MSCs group (n = 17): 100 μl culture medium containing 105 MSCs were injected into four sites of left ventricular free wall (25 μl per site); (iii) GENE group (n = 18): pCMVen-MLC2v-EGFP-VEGF165 plasmid [5 × 109 pfu (0.2 ml)] were injected into four sites of left ventricular free wall (0.05 ml per site)] and (iv) MSCs+GENE group (n = 17): rats received both myocardial MSCs and pCMVen-MLC2v-EGFP-VEGF165 plasmid injections. After 4 weeks, cardiac function was evaluated by echocardiography. Myocardial mRNA expressions of type I, type III collagen and transforming growth factor (TGF)-β1 were detected by RT-PCR. The protein expression of hVEGF165 was determined by Western blot. Myocardial protein expression of hVEGF165 was demonstrated in GENE and MSCs+GENE groups. Cardiac function was improved in MSCs, GENE and MSCs+GENE groups. Collagen volume fraction was significantly reduced and myocardial TGF-β1 mRNA expression significantly down-regulated in both GENE and MSCs+GENE groups, collagen type I/III ratio reduction was more significant in MSCs+GENE group than in MSCs or GENE group. Myocardial MSCs and hVEGF165 plasmid injection improves cardiac function possibly through down-regulating myocardial TGF-β1 expression and reducing the type I/III collagen ratio in this DCM rat model.

Significant Improvement in Ejection Fraction and Functional Class after Two Years of Cells Transplantation

“…The effect of improvement of cardiac functions in tissue regeneration and angiogenesis may be due to paracrine effect (inflammation) caused by hematopoietic and mesenchymal stem cells from bone marrow, stimulating the process of "homing" of macrophages, neutrophils, monocytes, stem cells and telocytes, and through transdifferentiation and differentiation of cells infused [1,6,14]. In the case of a paracrine effect, the first highlighted are macrophages can be induced stem cells for the production of nitrogen oxide (NO), it is important to induce angiogenesis, vasodilation and as an inducer of differentiation of stem cells into cardiomyocytes.…”

“…Idiopathic dilated cardiomyopathy (IDC) is a major public health problems in the Western world. In the United States, approximately 5.7 million people suffer from congestive heart failure, according to American Heart Association [1,2]. In addition, patients with IDC in functional class IV have high mortality.…”

“…In addition, patients with IDC in functional class IV have high mortality. To mitigate this problem in the world, are held about 16,000 transplants of autologous stem cells and 29,000 allogeneic [1,3]. In Brazil, the transplantation of autologous stem cells from bone marrow increases about 1000 cases per year [4].…”

“…Therefore, a therapy it is necessary to be able to improve heart function and more accessible to the population is of great interest. Thus, cell therapy with bone marrow stem cells have shown promising results in the literature as improvement of life of patients with IDC [1,8,12]. Thus, studies in ischemic heart disease demonstrated that stem cells obtained from various sources, including bone marrow may contribute to cardiac regeneration, also indicating the potential use of stem cell therapy in other cardiomyopathies [4,21].…”

Kangxianyixin Granule Improves Myocardial Fibrosis by Suppressing RhoA/ROCK1 Pathway

“…All of them were allowed free access to food and water. DCM group received a gavage of furazolidone (Tianjin Lisheng, China) solution (50 mg/ml, 0.3 mg/g for 8 weeks) [17]. Left ventricular end-diastolic diameter (LVEDD) and ejection fraction (LVEF) was measured by echocardiographic examination to con rm the model successful or not [18,19].…”