Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial

Background
Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls.
Aim
Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes.
Methods & Results
We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals.
Conclusion
Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction.

背景：近期，科研人员成功从人类胎儿与成人心脏中分离出心肌细胞祖细胞（cardiomyocyte progenitor cells, CMPCs）。在急性心肌梗死的实验小鼠模型中，直接心肌内注射人类心肌细胞祖细胞（human CMPCs, hCMPCs）可较对照组显著改善心脏功能。
研究目的：本研究旨在针对临床转化需求，探究经冠状动脉内输注胎儿来源hCMPCs的异种移植策略在慢性心肌梗死猪模型中的安全性与有效性。
方法与结果：本研究采用随机、双盲、安慰剂对照试验设计。在经皮左前降支动脉阻断90分钟造成缺血/再灌注损伤4周后，16头体重为68.5±5.4kg的猪接受了1000万胎儿hCMPCs的冠状动脉内输注或安慰剂处理。所有实验动物均使用环孢素（cyclosporin, CsA）进行免疫抑制。输注4周后，采用磁共振成像（MRI）进行的终点分析显示，两组间左心室射血分数、左心室舒张末期容积及左心室收缩末期容积均无显著差异。连续压力-容积（PV）环检测与超声心动图结果表明，在任意时间点，两组间的功能参数均无统计学差异。采用延迟强化磁共振成像（late gadolinium enhancement MRI）检测的随访阶段梗死面积，两组间亦无显著差异。细胞输注后30分钟的冠状动脉内压力与流量测量未发现冠状动脉阻塞征象。接受细胞治疗的动物未出现过早死亡事件。
结论：在慢性心肌梗死猪模型中，经冠状动脉内输注hCMPCs的异种移植策略具备可行性与安全性，但与安慰剂组相比，未显著改善左心室功能及缩小梗死面积。