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Differences in the Osteogenic Differentiation Capacity of Omental Adipose-Derived Stem Cells in Obese Patients With and Without Metabolic Syndrome

机译:肥胖患者有无代谢综合征的网膜脂肪干细胞成骨分化能力的差异

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摘要

Multiple studies have suggested that the reduced differentiation capacity of multipotent adipose tissue-derived mesenchymal stem cells (ASCs) in obese subjects could compromise their use in cell therapy. Our aim was to assess the osteogenic potential of omental ASCs and to examine the status of the isolated CD34negative-enriched fraction of omental-derived ASCs from subjects with different metabolic profiles. Omental ASCs from normal-weight subjects and subjects with or without metabolic syndrome were isolated, and the osteogenic potential of omental ASCs was evaluated. Additionally, osteogenic and clonogenic potential, proliferation rate, mRNA expression levels of proteins involved in redox balance, and fibrotic proteins were examined in the CD34negative-enriched fraction of omental-derived ASCs. Both the omental ASCs and the CD34negative-enriched fraction of omental ASCs from subjects without metabolic syndrome have a greater osteogenic potential than those from subjects with metabolic syndrome. The alkaline phosphatase and osteonectin mRNA were negatively correlated with nicotinamide adenine dinucleotide phosphate oxidase-2 mRNA and the mRNA expression levels of the fibrotic proteins correlated positively with nicotinamide adenine dinucleotide phosphate oxidase-5 mRNA and the homeostasis model assessment. Although the population doubling time was significantly higher in subjects with a body mass index of 25 kg/m2 or greater, only the CD34negative-enriched omental ASC fraction in the subjects with metabolic syndrome had a higher population doubling time than the normal-weight subjects. The osteogenic, clonogenic, fibrotic potential, and proliferation rate observed in vitro suggest that omental ASCs from subjects without metabolic syndrome are more suitable for therapeutic osteogenic applications than those from subjects with metabolic syndrome.
机译:多项研究表明,肥胖受试者中多能脂肪组织来源的间充质干细胞(ASC)的分化能力降低可能会损害其在细胞治疗中的用途。我们的目的是评估网膜ASCs的成骨潜能,并检查来自不同代谢谱的受试者网膜ASCs分离的CD34 阴性-富集部分的状态。从体重正常的受试者和有或没有代谢综合征的受试者中分离出大网膜ASC,并评估了大网膜ASC的成骨潜能。此外,在网膜来源的ASCs的CD34 sup -富集的部分中检测了成骨和克隆形成潜力,增殖速率,氧化还原平衡所涉及的蛋白的mRNA表达水平以及纤维化蛋白。没有代谢综合征的受试者的网膜ASC和网膜ASC的CD34 阴性-富集级分都比具有代谢综合征的受试者的网状ASC具有更大的成骨潜能。碱性磷酸酶和骨连接素mRNA与烟酰胺腺嘌呤二核苷酸磷酸氧化酶2 mRNA呈负相关,而纤维化蛋白的mRNA表达水平与烟酰胺腺嘌呤二核苷酸磷酸氧化酶5 mRNA和稳态模型评估呈正相关。尽管体重指数为25 kg / m 2 或更高的受试者的群体倍增时间明显更长,但受试者中只有CD34 阴性富集的网膜ASC分数高患有代谢综合症的人比正常体重的人拥有更长的人口倍增时间。体外观察到的成骨,克隆形成,纤维化潜能和增殖速率表明,没有代谢综合征的受试者的网膜ASC比具有代谢综合征的受试者的网膜ASC更适合治疗性成骨应用。

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