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鼠骨髓间充质干细胞的与年龄相关的分子遗传学变化。

Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells.

机构信息

Department of Molecular and Cellular Pharmacology, and the Vascular Biology Institute, University of Miami School of Medicine, Miami, FL 33136, USA.

出版信息

BMC Genomics. 2010 Apr 7;11:229. doi: 10.1186/1471-2164-11-229.

DOI:10.1186/1471-2164-11-229
PMID:20374652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2873471/
Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

间充质干细胞（MSC）是多能细胞，存在于骨髓和其他组织中，可以分化为所有胚层的细胞，可能参与成年生物体的组织维持和修复。由于其可塑性和可及性，这些细胞也是再生医学的首选候选者。干细胞衰老对机体衰老的贡献仍存在争议，一种理论认为，修复过程随着干细胞衰老和/或数量减少而恶化。年龄与骨髓间充质干细胞成骨和成脂潜能的变化有关。

结果

在这里，我们报告了从小鼠骨髓中分离的培养间充质干细胞的全基因组表达在 2、8 和 26 月龄时的变化。微阵列分析显示，超过 8000 个基因的表达发生了显著变化，多个分化、细胞周期和生长因子基因发生了阶段特异性变化。脂肪生成的关键标记物脂蛋白脂肪酶、FABP4 和 Itm2a 显示出与年龄相关的下降。主细胞周期调节剂 p53 和 p21 以及生长因子 HGF 和 VEGF 的表达也在 26 个月时显著下降。尽管骨髓分离后在体外进行了多次细胞分裂，但这些变化仍然明显。

结论

研究结果表明，间充质干细胞在衰老过程中会发生分子遗传变化，在培养过程中的传代中也会发生这些变化。这些变化可能会影响间充质干细胞的生理功能及其用于干细胞治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/f29be8d06033/1471-2164-11-229-14.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/1bff878be40b/1471-2164-11-229-9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/e9351e20d9dc/1471-2164-11-229-10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/f43f583ada9d/1471-2164-11-229-11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/f12d03a94889/1471-2164-11-229-12.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d20c/2873471/f29be8d06033/1471-2164-11-229-14.jpg

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