Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells.

Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells.
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衰老对小鼠Sca-1( )CD31(-)心脏干细胞活性的影响

DOI:
10.18632/oncotarget.13930
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发表时间:
2017-01-03
期刊:
影响因子:
--
通讯作者:
Zhou Z
Zhou Z
中科院分区:
其他
文献类型:
--
作者:
Wu Q;Zhan J;Pu S;Qin L;Li Y;Zhou Z

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心脏驻留干/祖细胞(CSC/CPCs)的治疗应用受到限制,由于其再生潜力随着供体年龄的下降。各种研究表明,心脏衰老是干细胞的问题,但年龄对CSC/CPCs亚群的影响、CSC/CPCs亚群衰老与年龄相关性功能障碍的关系却知之甚少。本研究以幼龄(2~ 3月龄)和老龄(22~ 24月龄)小鼠CSCs的Sca-1+ CD 31 −亚群为研究对象,采用特定培养基诱导14 d实现CSCs的生物学分化,诱导分化为心肌细胞、平滑肌细胞或内皮细胞,并对分化细胞结果进行免疫染色分析。通过流式细胞术测定细胞增殖和细胞周期,然后使用微阵列分析年轻和老年小鼠的变异性。虽然年龄较大的小鼠中CSC的数量较高,但高龄显著降低了向心脏细胞谱系的分化能力和增殖能力。衰老过程中CSC的Sca-1+ CD 31 −亚群的转录变化与维生素B6代谢、昼夜节律、酪氨酸代谢、补体和凝血级联反应有关。综合这些结果表明,心脏驻留干细胞/祖细胞在增殖、多能性和基因谱方面存在显着差异,并且这些差异取决于年龄。
Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31− subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31− subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.