Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction.
Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction.
复制标题
人间充质干细胞和ECFC联合移植可改善急性心肌梗塞后的心脏功能并减少心肌细胞凋亡。
DOI：
10.1007/s12015-022-10468-z
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发表时间：
2023
影响因子：
4.8
通讯作者：
Tarhuni,WadeaM
中科院分区：
文献类型：
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作者：
Tripathi,Himi;Domingues,Alison;Donahue,Renee;Cras,Audrey;Guerin,CoralieL;Gao,Erhe;Levitan,Bryana;Ratajczak,MariuszZ;Smadja,DavidM;Abdel-Latif,Ahmed;Tarhuni,WadeaM
非化学性心脏病通常由急性心肌梗死（AMI）引起，是世界范围内发病率和死亡率的主要原因之一。尽管医学和程序性治疗取得了重大进展，但每年仍有数百万AMI患者进展为心力衰竭。方法在急性心肌梗死的临床前模型中，我们研究了人间充质基质细胞（MSCs）和内皮集落形成细胞（ecfc）联合治疗减少早期缺血性损伤（MSCs）和增强血管生成（ecfc）的效果。NOD/SCID小鼠在AMI后单独或联合移植MSCs和ecfc。在短期和长期随访研究中评估心肌细胞凋亡和心功能恢复。结果AMI后1天，MSC-和ecfc处理的动物心肌细胞凋亡明显低于载药处理的动物。这一现象与AMI后4周梗死面积、心肌纤维化和心脏功能恢复的显著减少有关。结论在AMI的临床前模型中，与对照组相比，ecfc、MSCs以及两种细胞类型的联合使用可减少心肌细胞凋亡、疤痕大小和不良心脏重构。这些结果支持在缺血性心脏损伤急性期的未来人体研究中使用这种联合细胞治疗方法。图形抽象
BackgroundIschemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year.MethodsHere, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies.ResultsAt 1 day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4 weeks after AMI.ConclusionsThe use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury.Graphical abstract