Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis
Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis
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DOI：
10.1152/ajpheart.01071.2003
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发表时间：
2004-12-01
影响因子：
4.8
通讯作者：
Kitamura, S
中科院分区：
文献类型：
--
作者：
Nagaya, N;Fujii, T;Kitamura, S
间充质干细胞（Mesenchymal stem cells，MSCs）是一种多能细胞，可分化为多种细胞，包括心肌细胞和内皮细胞。然而，关于全身递送的MSC用于心肌梗死的治疗效力的信息很少。因此，我们研究了静脉内移植的MSC是否诱导血管生成和肌生成，并改善急性心肌梗死大鼠的心功能。从同基因成年大鼠的骨髓抽吸物中分离MSC并体外扩增。在冠状动脉结扎后3小时，向刘易斯大鼠静脉内施用5 × 10（6）MSC（MSC组，n = 12）或载体（对照组，n = 12）。移植的MSC优先被吸引到梗死区，而不是非梗死区，心肌。移植的MSC对心脏标志物：结蛋白、心肌肌钙蛋白T和连接蛋白43呈阳性。另一方面，部分移植的MSC呈血管性血友病因子阳性，并形成血管结构。MSC移植后毛细血管密度明显增加。MSC组的心肌梗死面积明显小于对照组（24 +/-2vs. 33 +/-2%，P < 0.05）。MSC移植组左室舒张末期压降低，左室最大dP/dt增加（均P < 0.05）。这些结果表明，静脉内施用MSC通过增强缺血心肌中的血管生成和肌生成来改善急性心肌梗死后的心功能。
Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into a variety of cells, including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. At 3 h after coronary ligation, 5 x 10(6) MSCs (MSC group, n = 12) or vehicle (control group, n = 12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted, but not the noninfarcted, myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size was significantly smaller in the MSC than in the control group (24 +/- 2 vs. 33 +/- 2%, P < 0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/dt (both P < 0.05 vs. control). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.