Comparison of Human Embryonic Stem Cell-Derived Cardiomyocytes, Cardiovascular Progenitors, and Bone Marrow Mononuclear Cells for Cardiac Repair.
Comparison of Human Embryonic Stem Cell-Derived Cardiomyocytes, Cardiovascular Progenitors, and Bone Marrow Mononuclear Cells for Cardiac Repair.
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DOI：
10.1016/j.stemcr.2015.09.011
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发表时间：
2015-11-10
影响因子：
5.9
通讯作者：
Murry CE
中科院分区：
文献类型：
--
作者：
Fernandes S;Chong JJH;Paige SL;Iwata M;Torok-Storb B;Keller G;Reinecke H;Murry CE
来源于人胚胎干细胞的心肌细胞（hESC-CMs）可以改善受损心脏的收缩力。我们假设，中胚层心血管祖细胞（hESC-CVP），能够产生血管细胞，除了心肌细胞，将提供上级修复心肌的多个组成部分。我们对hESC-CM和hESC-CVP进行了头对头比较，并将其与最常用的临床细胞类型人骨髓单核细胞（hBM-MNC）进行了比较。在心肌梗死的裸大鼠模型中，hESC-CM和hESC-CVP产生相当的移植物。两种方法同样改善了收缩功能和心室扩张。此外，只有罕见的人血管由hESC-CVP形成。hBM-MNC减弱心室扩张并增强宿主血管形成，而不植入长期或改善收缩性。因此，hESC-CM和CVP显示出类似的心脏修复功效，并且两者都比hBM-MNC更有效。然而，hESC-CVP不会在梗死心脏中形成更大的移植物或更显著数量的人血管。移植hBM-MNCs可以阻止梗死心脏的负性重塑hESC衍生的心血管祖细胞和永久性心肌细胞都改善了收缩性hBM-MNCs比hESC衍生的细胞导致更多的血管数量在本研究中，Murry和同事比较了三种有希望的心脏修复细胞来源对宿主心脏重塑和梗死大鼠心脏收缩功能的影响。移植后，人骨髓单个核细胞停止左心室收缩功能的恶化。相比之下，人胚胎干细胞（hESC）衍生的心血管祖细胞和永久性心肌细胞都改善了梗死心脏的收缩功能和负性重塑。
Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) can improve the contractility of injured hearts. We hypothesized that mesodermal cardiovascular progenitors (hESC-CVPs), capable of generating vascular cells in addition to cardiomyocytes, would provide superior repair by contributing to multiple components of myocardium. We performed a head-to-head comparison of hESC-CMs and hESC-CVPs and compared these with the most commonly used clinical cell type, human bone marrow mononuclear cells (hBM-MNCs). In a nude rat model of myocardial infarction, hESC-CMs and hESC-CVPs generated comparable grafts. Both similarly improved systolic function and ventricular dilation. Furthermore, only rare human vessels formed from hESC-CVPs. hBM-MNCs attenuated ventricular dilation and enhanced host vascularization without engrafting long-term or improving contractility. Thus, hESC-CMs and CVPs show similar efficacy for cardiac repair, and both are more efficient than hBM-MNCs. However, hESC-CVPs do not form larger grafts or more significant numbers of human vessels in the infarcted heart. Transplantation of hBM-MNCs can halt the negative remodeling of the infarcted heart Both hESC-derived cardiovascular progenitors and definitive cardiomyocytes improve contractility hBM-MNCs lead to greater vessel number than hESC-derived cells In the present study, Murry and colleagues compared the impact of three promising cellular sources for cardiac repair on host cardiac remodeling and contractile function of the infarcted rat heart. After transplantation, human bone marrow mononuclear cells halt the deterioration of left ventricular contractile function. In contrast, human embryonic stem cell (hESC)-derived cardiovascular progenitors and definitive cardiomyocytes both improved systolic function and negative remodeling of the infarcted hearts.