Data from: Intracoronary delivery of human mesenchymal/stromal stem cells: insights from coronary microcirculation invasive assessment in a swine model

Background: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. Objectives: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. Methods: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. Results: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. Conclusion: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

背景：间充质干细胞/基质细胞（Mesenchymal stem/stromal cells）具有利于临床应用的独特特性，已被研究用于心脏修复。然而，此类细胞体积大于冠状微血管，其经冠状动脉内递送时存在栓塞及微梗死风险的争议，该风险可能危及冠状动脉内给药途径的安全性与有效性。微循环阻力指数（index of microcirculatory resistance, IMR）是一种用于定量评估冠状微循环状态的有创检测方法。
研究目的：借助微循环阻力指数，探究间充质干细胞/基质细胞经冠状动脉内注射后心脏微循环的变化情况。
方法：将健康家猪随机分组，经冠状动脉内途径接受30×10^6个间充质干细胞，或仅含1%人白蛋白/磷酸盐缓冲液（PBS）的空白对照溶液（安慰剂组）。由盲态操作者在细胞输注前、输注后5分钟及30分钟时采集冠脉压力与血流数据，比较两组间的冠脉血流储备（coronary flow reserve, CFR）与IMR。
结果：冠脉血流储备与IMR的检测结果显示，静息状态下3次通过时间测量的变异系数为6%，最大充血状态下为11%。冠状动脉内输注后，两组间的冠脉血流储备无显著差异。注射间充质干细胞的实验组其IMR显著升高（输注后30分钟时为14.2U，安慰剂组为8.8U，p=0.02）；组内分析显示，从基线至细胞输注后30分钟，IMR显著升高112%，但未观察到心电图改变或临床恶化情况。
结论：综上，本研究在与人类心脏生理、功能及解剖结构高度相似的大型动物模型中，为间充质干细胞/基质细胞经冠状动脉内给药后会造成微循环障碍提供了确凿证据。