Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function

IF 3.8 3区 医学 Q2 CELL BIOLOGY
Michelle Maartens , Mare Vlok , Mari van de Vyver
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Abstract

Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lepob/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.
抗氧化剂提高糖尿病骨髓间充质干细胞的生存能力,但不损害其促再生分泌组功能
骨髓间充质干细胞(BM-MSC)功能障碍和生存能力差是糖尿病的突出问题,限制了其治疗效果。进行了蛋白质组学研究,以评估疾病相关的改变和抗氧化剂拯救细胞功能的功效。BM-MSCs是从肥胖糖尿病小鼠(B6.Cg-Lepob/J)中分离出来的,在n -乙酰半胱氨酸(NAC)和抗坏血酸-2磷酸(AAP)存在或不存在的情况下培养。无标签液相色谱和质谱(LC-MS)分析检测到5079个蛋白,其中251个蛋白在处理组之间存在差异表达。NAC/AAP通过上调参与氧化还原状态、ATP合成、Rho-GTPase信号传导的蛋白和调节BM-MSCs的免疫表型,提高分离后细胞的生长/活力。尽管分泌组的单一应用对糖尿病全层切除伤口的伤床再生没有任何好处,但细胞内蛋白质组揭示了NAC/AAP靶向呼吸链并调节脑基质间充质干细胞免疫表型的潜在作用机制。鉴于这些观察结果,补充抗氧化剂可能作为预防策略更有效地保护间充质干细胞免受功能衰退,而不是将其用作恢复剂,值得进一步研究。
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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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