Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy
Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy
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DOI：
10.3390/jcm2030103
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发表时间：
2013-09-01
影响因子：
3.9
通讯作者：
Boyle, Andrew J.
中科院分区：
文献类型：
--
作者：
Ye, Jianqin;Hom, Douglas S.;Boyle, Andrew J.
简介：微球（CS）是可以从心脏组织中生长的自组装细胞簇。它们含有异质细胞群，包括心脏祖细胞（CPC）和心脏成纤维细胞。CS和CPC在实验模型中已被证明可改善心肌梗死（MI）后的心脏功能，目前正在临床试验中进行研究。衰老对CS和CPC增殖能力的影响，以及细胞类型之间的旁分泌信号传导，仍然不完全清楚。方法和结果：我们比较了年轻和衰老小鼠心脏在基线和MI后CS的生长。年轻和老年心脏的CS数量在基线时相似。然而，心肌梗死后，年轻的心脏有一个显着增加CS的数量增长，但这种增殖反应心肌梗死几乎被取消在老龄化的心脏。此外，老化心脏中CS内CPC（定义为Sca-1（干细胞抗原-1）（+）/CD45（-））细胞的比例显著低于年轻心脏。因此，从老化心脏培养后可用的CPC数量明显低于年轻心脏。来自老化心脏的心脏成纤维细胞在培养中比来自年轻心脏的心脏成纤维细胞增殖更慢。然后，我们研究了老化的心脏成纤维细胞和CPC之间的相互作用。我们发现这些细胞类型之间的增殖没有显着的旁分泌效应，这表明受损的增殖是一个细胞自主的问题。结论：衰老的心脏产生较少的CPC，并且衰老的CPC在MI后具有显著降低的增殖潜力。衰老的心脏成纤维细胞增殖能力也降低，但这些似乎是细胞自主性问题，而不是由细胞类型之间的旁分泌信号传导引起的。
Introduction: Cardiospheres (CS) are self-assembling clusters of cells that can be grown from cardiac tissue. They contain a heterogeneous cell population that includes cardiac progenitor cells (CPCs) and cardiac fibroblasts. CS and CPCs have been shown to improve cardiac function after myocardial infarction (MI) in experimental models and are now being studied in clinical trials. The effects of aging on the proliferative capacity of CS and CPCs, and the paracrine signaling between cell types, remain incompletely understood. Methods and Results: We compared the growth of CS from young and aging murine hearts at baseline and following MI. The number of CS from young and aging hearts was similar at baseline. However, after MI, young hearts had a dramatic increase in the number of CS that grew, but this proliferative response to MI was virtually abolished in the aging heart. Further, the proportion of cells within the CS that were CPCs (defined as Sca-1(stem cell antigen-1)(+)/CD45(-)) was significantly lower in aging hearts than young hearts. Thus the number of available CPCs after culture from aging hearts was substantially lower than from young hearts. Cardiac fibroblasts from aging hearts proliferated more slowly in culture than those from young hearts. We then investigated the interaction between aging cardiac fibroblasts and CPCs. We found no significant paracrine effects on proliferation between these cell types, suggesting the impaired proliferation is a cell-autonomous problem. Conclusions: Aging hearts generate fewer CPCs, and aging CPCs have significantly reduced proliferative potential following MI. Aging cardiac fibroblasts also have reduced proliferative capacity, but these appear to be cell-autonomous problems, not caused by paracrine signaling between cell types.