Antioxidant Sirt1/Akt axis expression in resveratrol pretreated adipose‐derived stem cells increases regenerative capability in a rat model with cardiomyopathy induced by diabetes mellitus
Tung‐Sheng Chen, Shou‐Ying Chuang, Chia‐Yao Shen, Tsung‐Jung Ho, Ruey‐Lin Chang, Yu‐Lan Yeh, Chia‐Hua Kuo, B. Mahalakshmi, Wei‐Wen Kuo, Chih‐Yang Huang
Abstract
High-glucose (HG) suppresses mesenchymal stem cell (MSC) functions, resulting in a decrease in cardiac regenerative capability for MSC in diabetes mellitus (DM). Resveratrol enhances MSC functions under stress. This study explores if cardiac regenerative capability can be enhanced in MSCs pretreated with resveratrol in DM rats receiving MSCs. In vitro evidence confirms that HG decreases MSCs capability through suppression of survival markers, AMP-activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) axis, and expression of apoptotic markers. All of these markers are improved when MSCs are cocultured with resveratrol. Wistar male rats were randomly divided into Sham, DM (DM rats), DM rats with autologous transplantation of adipose-derived stem cells (DM + ADSC), and DM rats with resveratrol pretreated ADSC (DM + RSVL-ADSC). Compared to the Sham, DM induces pathological pathways (including fibrosis, hypertrophy, and apoptosis) and suppresses survival as well as the AMPK/Sirt1 axis in the DM group. DM + ADSC slightly improves the above pathways whereas DM + RSVL-ADSC significantly improves the above pathways when compared to the DM group. These results illustrate that resveratrol pretreated with MSCs may show clinical potential in the treatment of heart failure in patients with DM.