Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?
Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?
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DOI：
10.1016/j.jss.2008.03.054
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发表时间：
2009-04
期刊：
影响因子：
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通讯作者：
T. Markel;Paul R. Crisostomo;Maiuxi C Manukyan;Dalia Al-Azzawi;Christine M. Herring;T. Lahm;N. Novotny;D. Meldrum
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文献类型：
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作者：
T. Markel;Paul R. Crisostomo;Maiuxi C Manukyan;Dalia Al-Azzawi;Christine M. Herring;T. Lahm;N. Novotny;D. Meldrum
骨髓干细胞（BMSCs）可能是一种新的治疗器官缺血的方式，可能通过有益的旁分泌机制。然而，来自老年宿主的干细胞在应激期间表现出功能下降。因此，我们假设（1）来自新生宿主的BMSC将为缺血心肌提供保护，并且（2）新生干细胞将增强缺血后心肌恢复，高于成人干细胞治疗所见。材料和方法通过Langendorff分离的心脏制备，使雌性成年Sprague道利大鼠心脏经受缺血/再灌注方案（平衡15分钟，缺血25分钟，再灌注60分钟）。从成年和新生小鼠收获BMSC，并在正常条件下（37°C，5%CO2/空气）培养几代。在缺血之前，立即将一百万成人或新生儿BMSC输注到冠状动脉循环中。连续记录心功能参数，用成体BMSCs预处理显著增加缺血后心肌恢复，如左心室发展压、舒张末期压、收缩力和舒张率的改善。新生儿干细胞，但是，没有引起任何显着的改善心肌功能参数以下ischemia.CONCLUSIONNeonatal和成人骨髓间充质干细胞是明显不同的程度，他们可以提供有益的组织保护。本文的数据表明，存在一个关键年龄，当干细胞变得完全激活，以提供其有益的保护特性。定义启动这些保护特性的基因可能允许有益信号的遗传放大，以及产生为缺血组织提供最大保护的“超级干细胞”。
BACKGROUNDBone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that (1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium, and (2) neonatal stem cells would enhance postischemic myocardial recovery above that seen with adult stem cell therapy.MATERIALS AND METHODSFemale adult Sprague Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37°C, 5% CO2/air). Immediately prior to ischemia, one million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded.RESULTSPretreatment with adult BMSCs significantly increased postischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia.CONCLUSIONNeonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of “super stem cells” that provide maximum protection to ischemic tissues.