Barbash Israel M, Chouraqui Pierre, Baron Jack, Feinberg Micha S, Etzion Sharon, Tessone Ariel, Miller Liron, Guetta Esther, Zipori Dov, Kedes Laurence H, Kloner Robert A, Leor Jonathan
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel.
Circulation. 2003 Aug 19;108(7):863-8. doi: 10.1161/01.CIR.0000084828.50310.6A. Epub 2003 Aug 4.
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).
BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-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 99mTc-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.
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.
骨髓间充质干细胞（BM-MSCs）的全身递送是一种有吸引力的心肌修复方法。我们旨在在心肌梗死（MI）大鼠模型中测试该策略。
从大鼠骨髓中获取BM-MSCs，在体外扩增至纯度>50%，并用99mTc依沙美肟、荧光染料、LacZ标记基因或溴脱氧尿苷进行标记。大鼠通过短暂冠状动脉闭塞诱导心肌梗死或进行假心肌梗死手术。在心肌梗死后2天或10至14天，将99mTc标记的细胞（4×10⁶）输注到心肌梗死大鼠的左心室腔内，并与假心肌梗死大鼠或接受静脉输注治疗的心肌梗死大鼠进行比较。静脉输注4小时后，γ相机成像和离体器官计数显示，99mTc标记的细胞主要在肺部摄取，在肝脏、心脏和脾脏中的摄取量明显较小。与假心肌梗死心脏相比，通过左心室腔输注导致肺部摄取大幅降低，心脏摄取更好，尤其是梗死区域摄取更高。输注后1周的组织学检查在梗死或边界区域发现了标记细胞，但在远离的存活心肌或假心肌梗死心脏中未发现。在肺、肝、脾和骨髓中也发现了标记细胞。
心肌梗死后向大鼠全身静脉递送BM-MSCs虽然可行，但受供体细胞滞留在肺部的限制。直接左心室腔输注可增强细胞向缺血心肌的迁移和定植。
