Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells.
Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells.
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DOI：
10.1186/s13287-018-0825-1
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发表时间：
2018-04-06
影响因子：
7.5
通讯作者：
Sakaida I
中科院分区：
文献类型：
--
作者：
Fujisawa K;Hara K;Takami T;Okada S;Matsumoto T;Yamamoto N;Sakaida I
间充质干细胞(MSCs)是一种多能细胞，在再生医学中具有广阔的应用前景。然而，随着年龄的增长、异倍体细胞的增加、基因组的不稳定以及干细胞维持性的降低，需要更稳定的培养方法和更好的治疗效果的MSCs的生产。抗坏血酸(ASA)是多种酶的辅因子，具有抗氧化作用，某些动物(包括人类)无法合成抗坏血酸。然而，在骨髓间充质干细胞的培养中，对AsA的关注较少。通过基因表达系列分析和代谢组分析，分析了培养液中添加AsA对人MSCs增殖代谢的影响。我们发现，ASA促进了MSC的增殖，在扩增从骨髓中分离的MSCs时尤其有用。基因表达序列分析和代谢组分析表明，在没有AsA的培养中，由于使用AsA作为辅酶的酶活性降低而导致Hif1α的积累，Hif1α下游的基因得到了表达，并转化为模拟缺氧的代谢。AsA促进HIF1α分解，激活线粒体，影响细胞增殖和代谢。综合评价AsA对骨髓间充质干细胞各种代谢产物的影响，发现AsA可提高HIF1α羟基酶活性，抑制HIF1a转录，并导致线粒体激活。在MSC扩增过程中加入AsA可更有效地制备细胞。这些将为MSCs未来在再生医学中的应用提供重要的研究成果。本文的在线版本(10.1186/s13287-0180825-1)包含向授权用户提供的补充材料。
Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans. Nevertheless, little attention has been paid to AsA when culturing MSCs. We analyzed the effect of adding AsA to the culture medium on the proliferation and metabolism of human MSCs by serial analysis of gene expression and metabolome analysis. We found that AsA promotes MSC proliferation, and is particularly useful when expanding MSCs isolated from bone marrow. Serial analysis of gene expression and metabolome analysis suggested that, due to HIF1α accumulation caused by decreased activity of the enzymes that use AsA as a coenzyme in cultures without AsA, genes downstream of HIF1α are expressed and there is a conversion to a hypoxia-mimetic metabolism. AsA promotes HIF1α breakdown and activates mitochondria, affecting cell proliferation and metabolism. Comprehensive evaluation of the effects of AsA on various metabolic products in MSCs revealed that AsA increases HIF1α hydroxylase activity, suppressing HIF1a transcription and leading to mitochondrial activation. Adding AsA during MSC expansion leads to more efficient preparation of cells. These are expected to be important findings for the future application of MSCs in regenerative medicine. The online version of this article (10.1186/s13287-018-0825-1) contains supplementary material, which is available to authorized users.
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影响因子：
37.8
作者：
Takahashi, T;Lord, B;Lee, RT
通讯作者：
Lee, RT
维生素C在健康和疾病中的表观遗传作用。
DOI：
10.1007/s00018-016-2145-x
发表时间：
2016-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Camarena V;Wang G
通讯作者：
Wang G
影响因子：
7.4
作者：
Bartsch, Caroline;Bekhite, Mohamed M.;Wartenberg, Maria
通讯作者：
Wartenberg, Maria
DOI：
10.1016/j.bbrc.2009.12.096
发表时间：
2010-01-15
影响因子：
3.1
作者：
Jin, Yonghui;Kato, Tomohisa;Toguchida, Junya
通讯作者：
Toguchida, Junya
影响因子：
12.4
作者：
通讯作者：
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