在猪急性心肌梗死模型中，使用新型细胞递送系统（CIRCULATE导管）将人新生儿干细胞经冠状动脉转移至缺血心肌的安全性和有效性。
Safety and efficacy of transcoronary transfer of human neonatal stem cells to ischemic myocardium using a novel cell-delivery system (CIRCULATE catheter) in swine model of acute myocardial infarction.
作者信息
Bilewska Agata, Abdullah Mohamed, Mishra Rachana, Musialek Piotr, Gunasekaran Muthukumar, Saha Progyaparamita, Stefanowicz Artur, Mehta Vivek M, Sharma Sudhish, Kaushal Sunjay
机构信息
Department of Cardiothoracic Surgery, Ann and Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Cardiology and Internal Diseases, Military Institute of Medicine - National Research Institute, Warsaw, Poland.
出版信息
Postepy Kardiol Interwencyjnej. 2022 Dec;18(4):431-438. doi: 10.5114/aic.2022.121697. Epub 2022 Nov 30.
INTRODUCTION
Stem cell-based therapies have shown promise in adults with ischemic cardiomyopathy and children with congenital heart diseases, especially those without available therapeutic options. Human neonatal mesenchymal stem cells (nMSCs) have greater regenerative potential than adult stem cells.
AIM
To describe our experience with a novel catheter system for transcoronary delivery of cell-based therapies (CIRCULATE catheter) in the intra-coronary delivery of nMSCs in a swine acute myocardial infarct model.
MATERIAL AND METHODS
A newly developed catheter system (CIRCULATE catheter) with several unique features, including an expandable intra-coronary reservoir with spirally placed side holes of varying diameter, was used. nMSCs together with their secretome were used for the treatment. Pigs underwent myocardial infarction by inflating a 2.5 mm angioplasty balloon in the left anterior descending artery for 60 min. After reperfusion, stem cell therapy or placebo was administered via the novel catheter. TTE was performed at baseline, 1 h after the procedure, and before the euthanasia. Troponin blood concertation was evaluated at baseline, and after 48 h. The heart was harvested, sliced, and stained with triphenyl tetrazolium chloride (TTC). Infarct size to area-at-risk ratio was calculated. Troponin was assessed at baseline and after 48 h.
RESULTS
Thirty-nine pigs were operated with the mortality rate of 5.13% (exclusively malignant arrhythmia). Infarct size to area-at-risk ratio was significantly lower in the treatment group. Treated animals had higher ejection fraction than controls.
CONCLUSIONS
Intra-coronary delivery of neonatal mesenchymal stem cells reduces the infarct size and restores myocardial function in a swine model. The novel catheter system (CIRCULATE catheter) tested in this study was safe and effective in transcoronary cell delivery of human neonatal mesenchymal stem cells.
引言
基于干细胞的疗法在患有缺血性心肌病的成人和患有先天性心脏病的儿童中显示出了前景，尤其是那些没有可用治疗选择的患者。人类新生儿间充质干细胞（nMSCs）比成体干细胞具有更大的再生潜力。
目的
描述我们在猪急性心肌梗死模型中，使用一种新型导管系统（CIRCULATE导管）经冠状动脉递送基于细胞的疗法（即冠状动脉内递送nMSCs）的经验。
材料与方法
使用一种新开发的具有若干独特特征的导管系统（CIRCULATE导管），包括一个可扩张的冠状动脉内储液器，其带有螺旋排列的不同直径的侧孔。将nMSCs及其分泌组用于治疗。通过在左前降支动脉中充盈一个2.5毫米的血管成形术球囊60分钟，使猪发生心肌梗死。再灌注后，通过新型导管给予干细胞疗法或安慰剂。在基线、手术后1小时以及安乐死之前进行经胸超声心动图（TTE）检查。在基线以及48小时后评估肌钙蛋白血浓度。取出心脏，切片，并用氯化三苯基四氮唑（TTC）染色。计算梗死面积与危险面积之比。在基线和48小时后评估肌钙蛋白。
结果
39头猪接受了手术，死亡率为5.13%（均为恶性心律失常）。治疗组的梗死面积与危险面积之比显著更低。接受治疗的动物的射血分数高于对照组。
结论
在猪模型中，冠状动脉内递送新生儿间充质干细胞可减小梗死面积并恢复心肌功能。本研究中测试的新型导管系统（CIRCULATE导管）在经冠状动脉递送人类新生儿间充质干细胞方面是安全有效的。
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