Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium - Feasibility, cell migration, and body distribution
Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium - Feasibility, cell migration, and body distribution
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DOI：
10.1161/01.cir.0000084828.50310.6a
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发表时间：
2003-08-19
期刊：
影响因子：
37.8
通讯作者：
Leor, J
中科院分区：
文献类型：
--
作者：
Barbash, IM;Chouraqui, P;Leor, J
骨髓间充质干细胞（BM-MSCs）的全身移植是一种有吸引力的心肌修复方法。我们的目的是在心肌梗死（MI）后的大鼠模型中测试这种策略。方法和结果-从大鼠骨髓中获得BM-MSC，体外扩增至纯度> 50%，并用Tc-99 m exametazime、荧光染料、LacZ标记基因或溴脱氧尿苷标记。通过短暂性冠状动脉闭塞或假MI使大鼠遭受MI。在MI后2天或10 - 14天，将Tc-99 m标记的细胞（4 × 10（6））输注到MI大鼠的左心室腔中，并与假MI大鼠或静脉输注的MI大鼠进行比较。静脉输注后4小时，γ照相机成像和孤立器官计数显示Tc-99 m标记的细胞主要在肺中摄取，在肝、心和脾中摄取量显著较少。与假MI心脏相比，通过左心室腔输注的递送导致肺摄取显著降低，心脏摄取更好，并且特别是梗死的摄取更高。输注后1周的组织学检查在梗死区或边缘区发现标记细胞，但在远端存活心肌或假MI心脏中未发现标记细胞。标记的细胞也被确定在肺，肝，脾，和bone marrow. Conclusions全身静脉内输送BM-MSCs到大鼠MI后，虽然可行，是有限的截留供体细胞在肺部。直接左心室腔灌注可促进细胞向缺血心肌的迁移和定植。
Background-Systemic delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI).Methods and Results-BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with Tc-99m exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. Tc-99m-labeled cells (4x10(6)) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the Tc-99m-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow.Conclusions-Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.