Human cardiac stem cells
Human cardiac stem cells
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DOI：
10.1073/pnas.0706760104
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发表时间：
2007-08-28
影响因子：
11.1
通讯作者：
Anversa, Piero
中科院分区：
文献类型：
--
作者：
Bearzi, Claudia;Rota, Marcello;Anversa, Piero
哺乳动物心脏祖细胞的鉴定提出了人类心脏含有能够产生心肌细胞和冠状血管的干细胞群的可能性。人类心脏干细胞（hCSC）的表征对于衰竭心脏的治疗具有重要的临床意义。我们已经建立了从小心肌样本中分离和扩增 c-kit 阳性 hCSC 的条件。此外，我们还测试了这些细胞是否有能力在免疫功能低下的动物发生梗塞后形成功能正常的人类心肌。在这里，我们报告了体外鉴定出一类人类 c-kit 阳性心肌细胞，它们具有干细胞的基本特性：它们具有自我更新、克隆形成和多能性。 hCSC 主要分化为心肌细胞，并在较小程度上分化为平滑肌细胞和内皮细胞。当hCSC局部注射到免疫缺陷小鼠和免疫抑制大鼠的梗塞心肌中时，会产生嵌合心脏，其中包含由心肌细胞、冠状动脉阻力小动脉和毛细血管组成的人类心肌。人类心肌在结构和功能上与啮齿动物心肌相结合，有助于梗塞心脏的功能。分化的人类心脏细胞仅拥有一组人类性染色体，不包括细胞融合。 Cre-lox 策略证实了细胞融合的缺乏。因此，可以在体外分离和扩增 hCSC，以便随后对缺血性和非缺血性心力衰竭患者的死亡心肌进行自体再生。
The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immuno-suppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.