J Tissue Eng Regen Med. 2019 Jun 19. doi: 10.1002/term.2917. [Epub ahead of print]

Protective effect of autologous transplantation of resveratrol preconditioned adipose-derived stem cells in the treatment of diabetic liver dysfunction in rat model.

Chen TS¹, Ju DT², Day CH³, Yeh YL⁴, Chen RJ⁵, Viswanadha VP⁶, Chang RL⁷, Lin YC⁸, Yao CH^9,10, Huang CY^8,11,12,13.

Abstract

Previous studies stated that stem cell functions are reduced under high glucose environment, leading to reduce stem cell capability of tissue regeneration. This study aimed to investigate if stem cells preconditioned with resveratrol show better therapeutic effect on the treatment of liver dysfunction in diabetic rats than stem cells without resveratrol precondition. Male Wistar rats were divided into four groups including sham, DM (diabetic rats), DM+ADSC (DM rats receiving autologous transplantation of adipose-derived stem cells) and DM+pre-R-ADSC (DM rats receiving ADSC preconditioned with resveratrol). Compared to sham group, experimental results showed that DM group induced suppression of survival, suppression of Sirt1, activation of apoptotic and activation of fibrotic pathways, leading to liver dysfunction. Autologous transplantation of ADSC (DM+ADSC) improved above pathways except for fibrotic signaling. By contrast, transplantation of resveratrol preconditioned ADSC (DM+pre-R-ADSC) significantly improved above pathways including fibrosis. Supplemental evidences suggest that resveratrol precondition increases ADSC viability under high glucose stress via Sirt1 and IGF1R expressions. Furthermore, increased secretion of IGF1 via paracrine route also confirmed in ADSC preconditioned with resveratrol. The experimental results imply that ADSC preconditioned with resveratrol shows potential in the treatment of liver dysfunction in DM patients with liver dysfunction.