Formation of human myocardium in the rat heart from human embryonic stem cells
Formation of human myocardium in the rat heart from human embryonic stem cells
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DOI：
10.1016/s0002-9440(10)62041-x
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发表时间：
2005-09-01
影响因子：
6
通讯作者：
Murry, CE
中科院分区：
文献类型：
--
作者：
Laflamme, MA;Gold, J;Murry, CE
人类胚胎干细胞（hESC）提供了补充梗死后心脏中丢失的细胞的机会。我们探讨了是否可以通过将分化的心脏富集的hESC后代注射到无胸腺大鼠的左心室壁中来在大鼠心脏中产生人心肌。虽然最初的移植物主要是上皮细胞，但随着时间的推移，非心脏成分逐渐丢失，4周时移植物主要由心肌细胞组成。未观察到畸胎瘤元素。移植的心肌细胞富含糖原，并表达预期的心脏标志物，包括β-肌球蛋白重链，肌球蛋白轻链2 v和心房利钠因子。热休克处理使移植物尺寸提高了约三倍。心脏植入物表现出受体和移植物来源的大量血管生成。重要的是，在人类心肌细胞中的增殖比以前在啮齿动物来源的心肌细胞中观察到的更大：14.4%的移植心肌细胞表达增殖标记物Ki-67，2.7%在移植后4周掺入胸苷类似物BrdU。这种增殖与移植物大小在4周间隔内增加7倍有关。因此，hESC可以在大鼠心脏中形成人心肌，允许研究人心肌发育和生理学，并支持其用于心肌修复的可行性。
Human embryonic stem cells (hESCs) offer the opportunity to replenish cells lost in the postinfarct heart. We explored whether human myocardium could be generated in rat hearts by injecting differentiated cardiac-enriched hESC progeny into the left ventricular wall of athymic rats. Although initial grafts were predominantly epithelial, noncardiac elements were lost over time, and grafts consisted predominantly of cardiomyocytes by 4 weeks. No teratomatous elements were observed. Engrafted cardiomyocytes were glycogen-rich and expressed expected cardiac markers including beta-myosin heavy chain, myosin light chain 2v, and atrial natriuretic factor. Heat-shock treatment improved graft size approximately threefold. The cardiac implants exhibited substantial angiogenesis, both recipient and graft derived. Importantly, there was greater proliferation in human cardiomyocytes than previously seen in rodent-derived cardiomyocytes: 14.4% of graft cardiomyocytes expressed the proliferation marker Ki-67, and 2.7% incorporated the thymidine analog BrdU 4 weeks after transplantation. This proliferation was associated with a sevenfold increase in graft size over the 4-week interval. Thus, hESCs can form human myocardium in the rat heart, permitting studies of human myocardial development and physiology and supporting the feasibility of their use in myocardial repair.