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年龄和脂质过氧化对大鼠和人脂肪组织来源干细胞的影响。

Effect of Age and Lipoperoxidation in Rat and Human Adipose Tissue-Derived Stem Cells.

机构信息

Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain.

Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.

出版信息

Oxid Med Cell Longev. 2020 Dec 9;2020:6473279. doi: 10.1155/2020/6473279. eCollection 2020.

Abstract

A wide range of clinical applications in regenerative medicine were opened decades ago with the discovery of adult stem cells. Highly promising adult stem cells are mesenchymal stem/stromal cells derived from adipose tissue (ADSCs), primarily because of their abundance and accessibility. These cells have multipotent properties and have been used extensively to carry out autologous transplants. However, the biology of these cells is not entirely understood. Among other factors, the regeneration capacity of these cells will depend on both their capacity of proliferation/differentiation and the robustness of the biochemical pathways that allow them to survive under adverse conditions like those found in damaged tissues. The transcription factors, such as Nanog and Sox2, have been described as playing an important role in stem cell proliferation and differentiation. Also, the so-called longevity pathways, in which AMPK and SIRT1 proteins play a crucial role, are essential for cell homeostasis under stressful situations. These pathways act by inhibiting the translation through downregulation of elongation factor-2 (eEF2). In order to deepen knowledge of mesenchymal stem cell biology and which factors are determinant in the final therapeutic output, we evaluate in the present study the levels of all of these proteins in the ADSCs from humans and rats and how these levels are affected by aging and the oxidative environment. Due to the effect of aging and oxidative stress, our results suggest that before performing a cell therapy with ADSCs, several aspects reported in this study such as oxidative stress status and proliferation and differentiation capacity should be assessed on these cells. This would allow us to know the robustness of the transplanted cells and to predict the therapeutic result, especially in elder patients, where probably ADSCs do not carry out their biological functions in an optimal way.

摘要

几十年前,随着成体干细胞的发现,为再生医学的广泛临床应用开辟了道路。从脂肪组织(ADSCs)中分离出来的间充质干细胞/基质细胞具有很大的应用前景,主要是因为它们丰富且易于获得。这些细胞具有多能性,已被广泛用于进行自体移植。然而,这些细胞的生物学特性尚未完全被了解。除其他因素外,这些细胞的再生能力将取决于其增殖/分化能力以及使它们在受损组织等不利条件下生存的生化途径的稳健性。转录因子,如 Nanog 和 Sox2,已被描述为在干细胞增殖和分化中发挥重要作用。此外,所谓的长寿途径,其中 AMPK 和 SIRT1 蛋白起着至关重要的作用,对于应激条件下的细胞内稳态是必不可少的。这些途径通过下调伸长因子-2(eEF2)来抑制翻译。为了深入了解间充质干细胞生物学以及哪些因素对最终治疗效果起决定性作用,我们在本研究中评估了来自人类和大鼠的 ADSC 中所有这些蛋白质的水平,以及这些水平如何受到衰老和氧化环境的影响。由于衰老和氧化应激的影响,我们的结果表明,在进行 ADSC 细胞治疗之前,应该评估这些细胞的氧化应激状态以及增殖和分化能力等本研究中报道的几个方面。这将使我们了解移植细胞的稳健性,并预测治疗效果,特别是在老年患者中,ADSC 可能无法以最佳方式发挥其生物学功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/789b/7775166/26067e31f2d0/OMCL2020-6473279.001.jpg

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