【资源/摘要翻译】心肌缺血损伤可诱导心肌干细胞的激活

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. PNAS | June 14, 2005 | vol. 102 | no. 24 | 8692-8697
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 85-fold in acute infarcts and 25-fold in chronic infarcts. However, p16INK4a-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 26,000/cm3 of viable myocardium in acute to 7,000/cm3 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.
在这项研究中，我们检验了人心脏是否拥有促进梗死后心肌再生心肌干细胞池。为了这个目的，我们测定了20个急性心肌梗死的心脏、20个终末期梗死后心肌病的心脏和12个正常心脏的心肌干细胞生长和衰老的情况。结果发现急性心肌梗死心脏中的心肌干细胞数量明显增加，在终末期梗死后心肌病的心脏中亦较少程度的增加。通过端粒酶活性成分来确定干细胞的生长：急性心肌梗死的心脏增加到28%、终末期梗死后心肌病的心脏增加到14%（正常心脏为1.5%）；来源于心肌干细胞的心肌细胞、平滑肌细胞和内皮谱系细胞在急性心肌梗死心脏中和终末期梗死后心肌病的心脏中分别增加了约85倍和25倍。然而，代表衰老的p16INK4a-p53阳性心肌干细胞也同样增多（现急性心肌梗死：3.8%；终末期梗死后心肌病：9.6%；正常心脏：0.3%），使有功能活性的心肌干细胞的数量明显减少（急性心肌梗死：26，000/cm3；终末期梗死后心肌病：7，000/cm3）。在7个急性心肌梗塞的心脏中，自发再生的心肌细胞相互聚集而非相互融合。总之，人心脏拥有心肌干细胞池，并且心肌缺血损伤可诱导心肌干细胞的激活。有功能活性心肌干细胞的丢失或许可以作为慢性缺血性心肌病心功能进行性恶化和终末心力衰竭开始的标志。