School of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
J Tissue Eng Regen Med. 2019 Sep;13(9):1629-1640. doi: 10.1002/term.2917. Epub 2019 Aug 1.
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 with 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.
先前的研究表明,干细胞在高葡萄糖环境下的功能会降低,导致其组织再生能力下降。本研究旨在探讨经白藜芦醇预处理的干细胞在治疗糖尿病大鼠肝功能障碍方面是否比未经白藜芦醇预处理的干细胞具有更好的治疗效果。雄性 Wistar 大鼠被分为四组,包括假手术组、糖尿病组(糖尿病大鼠)、糖尿病+ADSC 组(糖尿病大鼠接受自体脂肪来源干细胞移植)和糖尿病+预-R-ADSC 组(糖尿病大鼠接受白藜芦醇预处理的 ADSC 移植)。与假手术组相比,实验结果表明,糖尿病组诱导了生存抑制、Sirt1 抑制、凋亡激活和纤维化途径激活,导致肝功能障碍。ADSC 的自体移植(糖尿病+ADSC)改善了上述途径,除了纤维化信号。相比之下,白藜芦醇预处理的 ADSC 移植(糖尿病+预-R-ADSC)显著改善了包括纤维化在内的上述途径。补充证据表明,白藜芦醇预处理通过 Sirt1 和 IGF1R 的表达增加了高葡萄糖应激下的 ADSC 活力。此外,通过旁分泌途径增加的 IGF1 分泌也在白藜芦醇预处理的 ADSC 中得到证实。实验结果表明,经白藜芦醇预处理的 ADSC 具有治疗糖尿病伴肝功能障碍患者肝功能障碍的潜力。