Anjum Muhammad Sohail, Mehmood Azra, Mahmood Faiza, Ali Muhammad, Tarrar Moazzam Nazir, Khan Shaheen N, Riazuddin Sheikh
National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan.
J Biosci. 2018 Sep;43(4):649-659.
Glucose-induced oxidative stress in the diabetic pancreas directly affects viability and the consequent therapeutic outcome of transplanted stem cells. Pretreatment of stem cells with growth factors induces tolerance in them against various stresses (hypoxia, thermal or hyperglycaemic). This study investigated the effect of pretreatment on insulin-producing cells (IPCs) differentiated from adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal cell-derived factor 1 alpha (SDF1 α) and basic fibroblast growth factor (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed that IPCs pretreated with a combination of SDF1α and bFGF exhibited maximally alleviated apoptosis, senescence and cell damage with a concomitantly increased release of insulin, enhanced cell proliferation and greater upregulation of Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose. These findings may offer an improved therapeutic outcome for the treatment of diabetes.
糖尿病胰腺中葡萄糖诱导的氧化应激直接影响移植干细胞的活力及后续治疗效果。用生长因子对干细胞进行预处理可诱导其对各种应激(缺氧、热应激或高血糖)产生耐受性。本研究调查了用基质细胞衍生因子1α(SDF1α)和碱性成纤维细胞生长因子(bFGF)联合预处理对源自脂肪间充质干细胞(ADMSC)分化的胰岛素生成细胞(IPC)抵抗高血糖应激(17或33 mM葡萄糖)的影响。结果显示,用SDF1α和bFGF联合预处理的IPC在受到33 mM葡萄糖应激时,凋亡、衰老和细胞损伤得到最大程度缓解,同时胰岛素释放增加、细胞增殖增强,胰岛素1、胰岛素2、神经源性分化因子3(Ngn3)、胰腺十二指肠同源盒1(Pdx1)和NK6转录因子相关蛋白2(Nkx6.2)的上调幅度更大。这些发现可能为糖尿病治疗带来更好的治疗效果。