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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity
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Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity

机译：同种异体间充质干细胞通过三系分化能力恢复慢性缺血性心肌病的心脏功能

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摘要

The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and α-sarcomeric actin. In addition, Ypos MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing to large and small vessel formation. Infarct size was reduced from 19.3 ± 1.7% to 13.9 ± 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 ± 1.7% to 41.3 ± 2.7% (P < 0.05) in MSC but not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment correlated with functional recovery in contractility (R = 0.85, P < 0.05) and MBF (R = 0.76, P < 0.01). Together these findings demonstrate long-term MSC survival, engraftment, and trilineage differentiation following transplantation into chronically scarred myocardium. MSCs are an adult stem cell with the capacity for cardiomyogenesis and vasculogenesis which contribute, at least in part, to their ability to repair chronically scarred myocardium.
机译：骨髓来源的间充质干细胞（MSC）心脏修复作用的潜在机制仍存在争议。在这里，我们测试了一种假设，即MSC通过包括长期植入和三系分化的机制再生了慢性梗塞的心肌。心肌梗死后十二周，雌性猪接受了基于导管的心内膜注射安慰剂（n = 4）或雄性同种异体MSC（2亿； n = 6）。对动物进行系列心脏磁共振成像，并通过将Y染色体（Y pos ）细胞与心脏，血管肌肉和内皮细胞谱系进行共定位来确定体内细胞的命运。通过与GATA-4，Nkx2.5和α-肌节肌动蛋白共定位，MSC移植到了梗塞区和边界区，并分化为心肌细胞。此外，Y pos MSCs表现出血管平滑肌和内皮细胞的分化，有助于大小血管的形成。在12岁以上的MSC中，梗死面积从19.3±1.7％减小到13.9±2.0％（P <0.001），射血分数（EF）从35.0±1.7％增加到41.3±2.7％（P <0.05）周。这伴随着区域收缩力和心肌血流量（MBF）的增加，尤其是在梗塞边界区域。重要的是，MSC的植入与收缩力（R = 0.85，P <0.05）和MBF（R = 0.76，P <0.01）的功能恢复相关。这些发现共同证明了移植到慢性瘢痕心肌中后MSC的长期存活，移入和三系分化。 MSC是具有心脏生成和血管生成能力的成年干细胞，其至少部分地有助于其修复慢性瘢痕心肌的能力。

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