Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
J Mol Med (Berl). 2011 Oct;89(10):947-59. doi: 10.1007/s00109-011-0769-8. Epub 2011 May 24.
Human ischemic cardiomyopathy is characterized by de novo cardiomyogenesis, which is limited to the surviving portion of the ventricle, and by organ hypertrophy that develops as a chronic response to ischemic injury. Although myocyte hypertrophy and myocyte regeneration restore the original myocardial mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired. Recently, vascular stem cells (VSCs) have been identified in the coronary circulation. VSCs express c-kit and the vascular endothelial growth factor receptor-2, KDR. These cells are self-renewing, clonogenic, and multipotent in vitro and in vivo. In animal models of critical coronary artery stenosis, VSCs form large conductive coronary arteries and their distal branches. This degree of vasculogenesis replaces partly the function of the occluded coronary artery improving myocardial perfusion and positively interfering with the development of the post-infarction myopathy. Cell therapy directed to the restoration of the integrity of the coronary circulation, the replacement of atherosclerotic coronary vessels, or both, would change dramatically the goal of cell therapy for the ischemic heart: the prevention of myocardial injury would become the end-point of cell therapy rather than the partial recovery of established damage.
人类缺血性心肌病的特征是新生心肌发生，新生心肌仅限于心室存活部分，以及作为对缺血性损伤的慢性反应发生的器官肥大。尽管心肌细胞肥大和心肌再生恢复了原始心肌质量，但冠状动脉仍然存在缺陷，心肌灌注的程度和调节严重受损。最近，在冠状动脉循环中已经鉴定出血管干细胞（VSCs）。VSCs 表达 c-kit 和血管内皮生长因子受体-2，KDR。这些细胞在体外和体内具有自我更新、克隆形成和多能性。在严重冠状动脉狭窄的动物模型中，VSCs 形成大的传导性冠状动脉及其远端分支。这种程度的血管发生部分替代了闭塞冠状动脉的功能，改善了心肌灌注，并积极干扰了梗死后心肌病的发展。针对恢复冠状动脉循环完整性、替代动脉粥样硬化冠状动脉或两者的细胞治疗，将极大地改变缺血性心脏病细胞治疗的目标：预防心肌损伤将成为细胞治疗的终点，而不是部分恢复已建立的损伤。
