Interleukin 10-Secreting MSCs via TALEN-Mediated Gene Editing Attenuates Left Ventricular Remodeling after Myocardial
Die Meng1, Seongho Han1, In Sil Jeong2
1Department of Family Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea.
Background/Aims:
Stem cells or progenitor cells have been demonstrated as a novel alternative for cell therapy; however, their sustained efficacy is still debated. This study aimed to evaluate whether interleukin 10 (IL-10) gene-edited amniotic mesenchymal stem cells (AMM/I) contribute to left ventricular (LV) function and remodeling after acute myocardial infarction (AMI).
Methods:
The IL-10 gene was integrated into the genomic locus of AMM via transcription activator-like effector nucleases (TALEN) and AMM/I were intramyocardially transplanted into AMI mice models. Cardiac function, quantitative polymerase chain reaction, histology, capillary density, and apoptosis assays were performed.
Results:
AMM/I transplantation significantly suppressed infiltrated CD68 positive or F4/80 positive inflammatory cells and reduced the expression of pro-inflammatory factors in the infarcted myocardium. In addition, significantly improved LV function and reduced infarct size was noted in mice model with AMM/I transplantation than in those given AMM. Moreover, AMM/I highly inhibited cell apoptosis and increased capillary density in the infarcted myocardium.
Conclusion:
Our study demonstrated that AMM/I recruitment played favorable roles in the early restoration of LV function and remodeling by suppressing inflammation and enhancing cardiac protection and capillary density.
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