Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

Abstract

Abstract. Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle and the third most common cause of heart failure. In the present study, we evaluated the effects of bone marrow-derived endothelial progenitor cell (EPC) transplantation on the development of DCM in a streptozotocin (STZ)-induced diabetic rat model. Ex vivo generated, characterized and cultivated rat EPCs were identified by flow cytometry of their surface markers. EPCs were transplanted intravenously into rats through the tail vein 6 weeks after they were challenged with STZ and the rats were sacrificed 4 weeks later. Before sacrifice, left ventricular (LV) catheterization was performed to evaluate the cardiac function. Myocardium sections were stained with Masson's trichrome staining to investigate myocardial collagen contents. Fibrosis-, apoptosis-and oxidative stress-related gene expressions were analyzed by western blot analysis. Transplantation of EPCs alleviated the impaired cardiac function associated with diabetes and decreased the collagen volume in diabetic myocardium resulting in improved cardiac function. Furthermore, EPC transplantation decreased the expression of type I collagen, Bax, caspase-3 and p67phox, while increasing the expression of Bcl-2 and manganese superoxide dismutase (MnSOD). Taken together, our results suggest that transplantation of EPCs improved cardiac function in the rat DCM model, likely through inhibition of cardiomyocyte apoptosis and attenuating myocardial fibrosis.

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“…These cells were called late EPCs, and we used late EPCs for further studies. EPCs expressed surface markers, such as CD31 (96.8±0.5%), CD34 (97.2±1.4%), CD133 (92.8±5.3%) and VEGFR-2 (91.5±3.7%) ( Figure 1C), and this finding is consistent with previous studies [20,21]. EPCs could differentiate into adipocytes ( Figure 1D) and smooth muscle cells ( Figure 1E).…”

Decreased Circulating Endothelial Progenitor Cell Levels in Patients with Heart Failure with Preserved Ejection Fraction

“…Our findings provide pathophysiological insights into HFpEF development and raise the possibility that circulating EPCs may be a target for preventive interventions in selected individuals. Transplantation or an increased circulating EPC count may attenuate heart failure progression [36,37]. Further studies are needed to determine whether an increased circulating EPC count can improve cardiac outcomes in HF patients.…”

Diabetic cardiomyopathy: where we are and where we are going

“…Specific mi-RNA targets are useful for the treatment of structural heart disease in mice [138]. Similarly, the transplantation of bone marrow-derived endothelial progenitor cells (stem cell therapy) ameliorates DCM in rat models [139]. Ongoing investigations may help us to translate the success of these experimental models into clinical practice in the future.…”