Early improvement in cardiac tissue perfusion due to mesenchymal stem cells
Early improvement in cardiac tissue perfusion due to mesenchymal stem cells
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DOI：
10.1152/ajpheart.00762.2007
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发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Hare, Joshua M.
中科院分区：
文献类型：
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作者：
Schuleri, Karl H.;Amado, Luciano C.;Hare, Joshua M.
心肌梗死（MI）后间充质干细胞（MSC）治疗改善左心室功能（LV）的潜在机制仍然存在高度争议。心肌再生和新血管形成导致组织灌注增加，是被提出的机制。本研究证明，在猪模型中，心肌梗死后3天给予间充质干细胞增加了组织灌注，从而改善了左室功能。阻断猪左冠状动脉前降支60分钟，再灌注心肌梗死。猪被分配接受心肌内注射同种异体间充质干细胞（2亿个，类似于15次注射）（n = 10），安慰剂（n = 6），或不干预（n = 8）。静息心肌血流量（MBF）通过首次灌注磁共振成像（MRI）连续评估8周。在第1周内，mscs处理的猪梗死区静息MBF较安慰剂注射和未治疗的动物增加[分别为0.17 +/- 0.03,0.09 +/- 0.01和0.08 +/- 0.01，心肌梗死与左心室血池（LVBP）的信号强度比；P < 0.01 vs安慰剂，P < 0.01 vs未治疗]。相比之下，三组在第4周和第8周的信号强度比无法区分。然而，在第8周，msc处理的动物在梗死区表现出更大、更成熟的血管和更少的凋亡，并改善了局部和整体左室功能。总之，这些发现表明，在msc处理的心脏中，早期组织灌注的增加早于左室功能的改善和细胞凋亡的减少。基于心脏mri的血流测量可能是预测骨髓间充质干细胞治疗后成功的心肌再生过程的有用工具。
The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, similar to 15 injections) (n = 10), placebo (n = 6), or no intervention (n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 +/- 0.03, 0.09 +/- 0.01, and 0.08 +/- 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment.