Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.
Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.
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DOI：
10.1186/1471-2164-11-229
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发表时间：
2010-04-07
期刊：
影响因子：
4.4
通讯作者：
Webster KA
中科院分区：
文献类型：
--
作者：
Wilson A;Shehadeh LA;Yu H;Webster KA
间充质干细胞（MSC）是一种多能细胞，存在于骨髓和其他组织中，可以分化为所有胚层细胞，并可能参与成人组织的维持和修复。由于它们的可塑性和可获得性，这些细胞也是再生医学的主要候选者。干细胞老化对机体衰老的贡献存在争议，一种理论认为修复过程恶化是干细胞老化和/或数量减少的结果。年龄与间充质干细胞成骨和成脂潜能的变化有关。在这里，我们报告了从2个月、8个月和26个月大的小鼠骨髓中分离的培养MSCs的整体基因表达的变化。微阵列分析显示，超过8000个基因的表达发生了显著变化，其中多分化、细胞周期和生长因子基因的表达发生了阶段性变化。脂肪生成的关键标志物包括脂蛋白脂肪酶、FABP4和Itm2a显示出年龄依赖性下降。主细胞周期调节因子p53和p21以及生长因子HGF和VEGF的表达在26个月时也显著下降。骨髓分离后，尽管体外细胞多次分裂，这些变化仍很明显。结果表明，MSCs在衰老过程中受到分子遗传变化的影响，这些变化在培养传代过程中被保存下来。这些变化可能会影响自体间充质干细胞的生理功能和干细胞治疗潜力。
Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.
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影响因子：
--
作者：
Kretlow JD;Jin YQ;Liu W;Zhang WJ;Hong TH;Zhou G;Baggett LS;Mikos AG;Cao Y
通讯作者：
Cao Y
影响因子：
37.8
作者：
Farrington-Rock, C;Crofts, NJ;Canfield, AE
通讯作者：
Canfield, AE
DOI：
10.1152/ajpregu.2001.280.6.r1772
发表时间：
2001-06-01
影响因子：
2.8
作者：
Karagiannides, I;Tchkonia, T;Kirkland, JL
通讯作者：
Kirkland, JL
影响因子：
11.2
作者：
Bang, OY;Lee, JS;Lee, G
通讯作者：
Lee, G
影响因子：
10.6
作者：
Edwards DR;Handsley MM;Pennington CJ
通讯作者：
Pennington CJ