High glucose-induced reactive oxygen species generation promotes sternness in human adipose-derived stem cells
High glucose-induced reactive oxygen species generation promotes sternness in human adipose-derived stem cells
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DOI：
10.1016/j.jcyt.2015.11.012
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发表时间：
2016-03-01
期刊：
影响因子：
4.5
通讯作者：
Young, Tai-Horng
中科院分区：
文献类型：
--
作者：
Cheng, Nai-Chen;Hsieh, Tsung-Yu;Young, Tai-Horng
背景目标。脂肪干细胞(ASCs)是治疗糖尿病并发症的细胞治疗的重要来源。然而，高血糖可能会改变一些细胞功能，因此本研究旨在探讨糖尿病环境对ASCs的严谨性和分化能力的影响。方法：研究方法。从糖尿病患者皮下脂肪组织(DASCs)和非糖尿病供者皮下脂肪组织(NASCs)中获得人ASCs，并对其进行鉴定。为建立体外高血糖环境，将神经干细胞置于长期高糖(HG；4.5g/L)和低糖(Lg；1.0g/L)条件下培养。结果。细胞表面标志物在dASCs和NASC中的表达相似，具有间充质干细胞的特征。虽然dASCs或HG处理的nASCs增殖减少，但多能标志物SOX-2、Oct-4和Nanog的表达增强。此外，HG处理的nASCs表现出细胞迁移减少，衰老加快，细胞内活性氧(ROS)显著升高，而其成脂和成骨分化能力与LG处理的细胞相当。经抗氧化剂处理后，HG处理的nASCs细胞增殖活性增强，但细胞毒性未见增强。HG诱导的这种生物学反应与ROS介导的AKT衰减有关。在适当的诱导条件下，HG处理的nASCs和dASCs向神经元样细胞的转分化潜能增强。讨论。尽管在糖尿病环境中，ASCs的增殖活性较低，衰老程度较高，但通过ROS介导的机制，ASCs也表现出更强的刺激性和神经源性转分化潜力。这一信息对未来糖尿病患者自体ASCs的应用具有重要意义。
Background aims. Adipose-derived stem cells (ASCs) represent an important source of cell therapy to treat diabetic complications. However, hyperglycemia may alter several cellular functions, so the present study aimed to investigate the influence of a diabetic environment on the sternness and differentiation capabilities of ASCs. Methods. Human ASCs were obtained from subcutaneous adipose tissues of diabetic (dASCs) and nondiabetic donors (nASCs) and characterized. To reproduce an in vitro hyperglycemia environment, the nASCs were also cultured under prolonged high-glucose (HG; 4.5 g/L) or low glucose (LG; 1.0 g/L) conditions. Results. The expression of cell surface markers in dASCs and nASC was similar and characteristic of mesenchymal stem cells. Although dASCs or HG-treated nASCs exhibited decreased proliferation, enhanced expression of the pluripotent markers Sox-2, Oct-4, and Nanog was observed. Moreover, HG-treated nASCs exhibited decreased cell migration, enhanced senescence, and significantly higher intracellular reactive oxygen species (ROS), whereas their adipogenic and osteogenic differentiation capacities remained comparable to LG-treated cells. With antioxidant treatment, HG-treated nASCs showed improved cell proliferative activity without sternness enhancement. This HG-induced biological response was associated with ROS-mediated AKT attenuation. When cultured in an appropriate induction medium, the HG-treated nASCs and dASCs exhibited enhanced potential of transdifferentiation into neuron-like cells. Discussion. Despite lower proliferative activity and higher senescence in a diabetic environment, ASCs also exhibit enhanced sternness and neurogenic transdifferentiation potential via a ROS-mediated mechanism. The information is important for future application of autologous ASCs in diabetic patients.