Texas Heart Institute, St. Luke's Episcopal Hospital, Houston, TX, USA,
Mol Biotechnol. 2013 Oct;55(2):169-78. doi: 10.1007/s12033-013-9668-2.
The availability of glucose and oxygen are important regulatory elements that help directing stem cell fate. In the undifferentiated state, stem cells, and their artificially reprogrammed equivalent-induced pluripotent stem cells (iPS) are characterized by limited oxidative capacity and active anaerobic glycolysis. Recent studies have shown that pluripotency-a characteristic of staminality-is associated with a poorly developed mitochondrial patrimony, while differentiation is accompanied by an activation of mitochondrial biogenesis. Besides being an important energy source in hypoxia, high glucose level results in hyperosmotic stress. The identification of specific metabolic pathways and biophysical factors that regulate stem cell fate, including high glucose in the extracellular medium, may therefore facilitate reprogramming efficiency and control the differentiation and fate of iPS cells, which are increasingly being explored as therapeutic tools. In this article, we review recent knowledge of the role of glucose metabolism and high glucose level as major anaerobic energy source, and a determinant of osmolarity as possible tools for reprogramming therapies in clinical applications. As in the diabetic setting hyperglycemia negatively affect the stem/progenitor cell fate and likely somatic reprogramming, we also discuss the in vivo potential transferability of the available in vitro findings.
葡萄糖和氧气的供应是指导干细胞命运的重要调节因素。在未分化状态下，干细胞及其人工重编程得到的诱导多能干细胞（iPS）的特点是氧化能力有限，而无氧糖酵解活跃。最近的研究表明，多能性——干细胞特性之一——与线粒体遗产的发育不良有关，而分化伴随着线粒体生物发生的激活。除了在缺氧条件下是重要的能量来源外，高葡萄糖水平还会导致高渗应激。因此，确定调节干细胞命运的特定代谢途径和生物物理因素，包括细胞外培养基中的高葡萄糖，可能会提高重编程效率，并控制 iPS 细胞的分化和命运，这些细胞作为治疗工具正越来越多地被探索。在本文中，我们回顾了葡萄糖代谢和高葡萄糖水平作为主要无氧能量来源的最新知识，以及渗透压作为可能的重编程治疗工具的决定因素，这些都可能在临床应用中得到应用。正如在糖尿病环境中高血糖会对干细胞/祖细胞命运和可能的体细胞重编程产生负面影响一样，我们还讨论了现有体外研究结果在体内的潜在可转移性。
