Combined treatment with systemic resveratrol and resveratrol preconditioned mesenchymal stem cells, maximizes antifibrotic action in diabetic cardiomyopathy.
Asmaa Mohammed ShamsEldeenHend AshourHeba Samy ShoukryMostafa FadelSamaa Samir KamarMarwan AabdelbasetLaila Ahmed RashedHania Ibrahim AmmarPublished in: Journal of cellular physiology (2018)
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.
Keyphrases
- respiratory syncytial virus
- mesenchymal stem cells
- respiratory tract
- umbilical cord
- type diabetes
- cell proliferation
- wound healing
- stem cells
- left ventricular
- bone marrow
- ejection fraction
- heart failure
- oxidative stress
- magnetic resonance imaging
- glycemic control
- machine learning
- cell therapy
- cell death
- skeletal muscle
- pulmonary hypertension
- adipose tissue
- atrial fibrillation
- newly diagnosed
- liver fibrosis
- big data
- replacement therapy
- data analysis
- aortic stenosis
- subarachnoid hemorrhage