Diabetes is a complex multifactorial disorder associated with hyperglycemia, oxidative stress, and inflammation. The pathological microenvironment impairs mesenchymal stem cell (MSC) viability and dysregulates their proregenerative and immune-modulatory function causing maladaptive tissue damage. Targeting stem cells to protect them against impairment could thus delay the onset of complications and enhance the quality of life in diabetes mellitus patients. The aim of this study was to investigate the efficacy of N-acetylcysteine (NAC) and ascorbic-acid-2-phosphate (AAP) oral supplementation as preventative measure against MSC impairment. Healthy wild-type control (C57BL/6J) (male, n = 24) and obese diabetic (B6.C-Lep^ob/J) (ob/ob) (male, n = 24) mice received either placebo or antioxidant (NAC/AAP) supplementation for a period of 6 weeks. Metabolic parameters (weight and blood glucose) and the oxidative status (serum total serum antioxidant capacity, malondialdehyde) of animals were assessed. At the end of the 6-week supplementation period, bone marrow MSCs were isolated and their functionality (growth rate, viability, adipogenesis, and osteogenesis) assessed ex vivo. Real time quantitative polymerase chain reaction microarray analysis was also performed to assess the expression of 84 genes related to oxidative stress in MSCs. Despite no change in the metabolic profile, NAC/AAP supplementation improved the antioxidant status of diabetic animals and reduced lipid peroxidation, which is indicative of cellular damage. NAC/AAP also improved the population doubling time of MSCs (first 6-days postisolation) and significantly downregulated the expression of two genes (Nox1 and Rag2) associated with oxidative stress compared to placebo treatment. Taken together, this study has shown reduced oxidative stress and improvements in MSC function following in vivo antioxidant supplementation in healthy control and type 2 diabetic mice.

中文翻译：

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N-乙酰半胱氨酸和抗坏血酸-2-磷酸补充剂对 B6.C-Lepob/J 2 型糖尿病小鼠间充质干细胞功能的影响

糖尿病是一种复杂的多因素疾病，与高血糖、氧化应激和炎症有关。病理性微环境会损害间充质干细胞 (MSC) 的活力并失调其促再生和免疫调节功能，从而导致适应不良的组织损伤。因此，靶向干细胞以保护它们免受损害可以延缓并发症的发生并提高糖尿病患者的生活质量。本研究的目的是研究 N-乙酰半胱氨酸 (NAC) 和抗坏血酸-2-磷酸 (AAP) 口服补充剂作为 MSC 损伤预防措施的功效。健康的野生型对照 (C57BL/6J) (男性, n  = 24) 和肥胖糖尿病 (B6.C-Lep ^ob /J) (ob/ob) (男性, n = 24) 小鼠接受安慰剂或抗氧化剂 (NAC/AAP) 补充剂 6 周。评估了动物的代谢参数（体重和血糖）和氧化状态（血清总血清抗氧化能力、丙二醛）。在 6 周补充期结束时，分离出骨髓 MSC，并在体外评估其功能（生长速率、活力、脂肪生成和成骨）。还进行了实时定量聚合酶链反应微阵列分析以评估 84 个与 MSCs 中氧化应激相关的基因的表达。尽管代谢特征没有变化，但 NAC/AAP 补充剂改善了糖尿病动物的抗氧化状态并减少了脂质过氧化，这表明细胞损伤。与安慰剂治疗相比， Nox1和Rag2与氧化应激相关。总之，这项研究表明，在健康对照和 2 型糖尿病小鼠体内补充抗氧化剂后，氧化应激降低并改善了 MSC 功能。