Key result
Combined treatment with systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells improved ejection fraction (median 81.50%) and attenuated fibrosis in diabetic rats.
Why the study?
Because the Wnt/β-catenin signaling pathway plays a crucial role in diabetic cardiomyopathy, the authors aimed to investigate systemic resveratrol, alone and combined with nonconditioned or resveratrol-preconditioned mesenchymal stem cells, on this pathway in streptozotocin-induced diabetic cardiomyopathy.
Does combined treatment with systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells improve cardiac function and reduce fibrosis in a rat model of diabetic cardiomyopathy?
Does combined treatment with systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells improve cardiac function and reduce fibrosis in a rat model of diabetic cardiomyopathy?
Combined treatment with systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells maximizes antifibrotic effects and improves cardiac function in a rat model of diabetic cardiomyopathy.
Hypothesis-generating for combined resveratrol-MSC therapy in diabetic cardiomyopathy; human trials needed before clinical adoption.
Wnt/β-catenin signaling pathway plays a crucial role in diabetic cardiomyopathy (DCM), thus we aimed at investigating the effect of one therapeutic approach with resveratrol (RSV) given systemically and combined treatment of RSV with mesenchymal stem cells (MSCs) that was either RSV-preconditioned or not on Wnt/β-catenin signaling pathway in streptozotocin-induced DCM, and to evaluate effects of RSV preconditioning on MSCs therapeutic potential. The rats were divided into control (C, n = 8), diabetic (DM, n = 8), diabetic treated with systemic RSV (DM-RSV, n = 8), diabetic treated with RSV and nonconditioned MSCs (DM-RSV-MSCs, n = 8), diabetic treated with RSV and RSV-incubated with MSCs (DM-RSV-MSCc, n = 8) and diabetic treated with RSV-conditioned MSCs (DM-MSCc, n = 8). Echocardiography (Echo) showed significant improvement of cardiac functions in all groups treated with RSV either systemic or added in culture media. Data of ejection fraction (EF%) of DM-RSV-MSCc (81.50; interquartile range [IQR], 80.00-83.00) was comparable to both DM-RSV-MSCs (77.50; IQR, 71.50-79.00), and DM-MSCc (71.50; IQR, 70.00-74.50). Histological examination of the left ventricles was performed for all groups. DM group revealed significant myocardial hypertrophy, apoptosis, interstitial fibrosis, and microvascular affection. All treated groups were associated, in variable degrees, with attenuation of cardiac hypertrophy and fibrosis, decreased area% for cardiac immunostaining of secreted frizzled-related protein (sFRP2) and Wnt/β-catenin and improvement of the microvasculature. In conclusion, MSCs pretreated with resveratrol for 7 days showed increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and combined use of RSV (systemically and in culture media) significantly could improve cardiac remodeling capacity of MSCs via attenuation of sFRP2-mediated fibrosis and the downstream Wnt/β-catenin pathway.
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ShamsEldeen et al. (2018) studied Diabetic cardiomyopathy (n=48). Systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells vs. Control, untreated diabetic, and other treatment combinations was evaluated on Ejection fraction (EF%). Combined treatment with systemic resveratrol and resveratrol-preconditioned mesenchymal stem cells improved ejection fraction (median 81.50%) and attenuated fibrosis in diabetic rats.
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