Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure
Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure
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DOI：
10.1073/pnas.0500169102
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发表时间：
2005-06-14
影响因子：
11.1
通讯作者：
Anversa, P
中科院分区：
文献类型：
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作者：
Urbanek, K;Torella, D;Anversa, P
在这项研究中，我们测试了人类心脏是否具有促进梗死后再生的心脏干细胞（CSC）库。为了这个目的，CSC的生长和衰老进行了测量，在20个心脏与急性梗死，20个心脏与终末期心肌梗死后心肌病，和12个对照心脏。CSC数量在急性梗死中显著增加，在较小程度上，在慢性梗死中。CSC的生长与端粒酶活性的分化CSC的增加相关，从对照组的1.5%增加到急性梗死组的28%和慢性梗死组的14%。CSC有丝分裂指数在急性梗死中增加29倍，在慢性梗死中增加14倍。在急性梗死中，向肌细胞、平滑肌和内皮细胞谱系定向的CSC增加约85倍，在慢性梗死中增加约25倍。然而，p16（INK 4a）-p53-阳性衰老CSC也增加，在对照组、急性梗死组和慢性梗死组中分别为10%、18%和40%。在对照组、急性梗死组和慢性梗死组中，老年CSC的端粒较短，凋亡分别涉及0.3%、3.8%和9.6%的CSC。这些变量分别使功能正常的CSC数量从急性存活心肌的约26，000/cm 3减少到慢性梗死的约7，000/cm 3。在7例急性梗死中，发现了不涉及细胞融合的自发性心肌再生灶。总之，人类心脏具有CSC隔室，并且CSC激活响应于缺血性损伤而发生。慢性缺血性心肌病中功能活性CSC的丧失可能是进行性功能恶化和终末衰竭发生的基础。
In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased approximate to 85-fold in acute infarcts and approximate to 25-fold in chronic infarcts. However, p16(INK4a)-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from approximate to 26,000/cm(3) of viable myocardium in acute to approximate to 7,000/cm(3) in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.