Stem cell-based therapy is one of the most attractive approaches to ischemic heart diseases such as myocardial infarction (MI). We evaluated the cardio-protective effects of the hUCB-MSCs stably expressing LEF1 (LEF1/hUCB-MSCs) in a rat model of MI. LEF1 overexpression in hUCB-MSCs promoted cell proliferation and anti-apoptotic effects in hypoxic conditions. For the application of its therapeutic effects in vivo, the LEF1 gene was introduced into an AAVS1 locus known as a safe harbor site on chromosome 19 by CRISPR/Cas9-mediated gene integration in hUCB-MSCs. Transplantation of LEF1/hUCB-MSCs onto the infarction region in the rat model significantly improved overall survival. The cardio-protective effect of LEF1/hUCB-MSCs was proved by echocardiogram parameters including greatly improved left ventricle ejection fraction (EF) and fractional shortening (FS). Moreover, histology and immunohistochemistry successfully presented reduced MI region and fibrosis by LEF1/hUCB-MSCs. We found that this overall positive effects of LEF1/hUCB-MSCs are attributed by increased proliferation and survival of stem cells in oxidative stress conditions and by the secretion of various growth factors by LEF1. In conclusion, this study suggests that the stem cell-based therapy conjugated with genome editing of transcription factor LEF1, which promotes cell survival, could be an effective therapeutic strategy for cardiovascular disease.

基于干细胞的疗法是治疗缺血性心脏病（如心肌梗塞（MI））最有吸引力的方法之一。我们评估了稳定表达LEF1的hUCB-MSCs（LEF1 / hUCB-MSCs）在MI大鼠模型中的心脏保护作用。在低氧条件下，hUCB-MSC中的LEF1过表达促进细胞增殖和抗凋亡作用。对于其体内治疗作用的应用，通过hUCB-MSC中CRISPR / Cas9介导的基因整合，将LEF1基因引入AAVS1基因座，该基因座被称为19号染色体上的安全港位点。LEF1 / hUCB-MSCs移植到大鼠模型中的梗塞区域显着改善了总生存期。超声心动图参数证明了LEF1 / hUCB-MSC的心脏保护作用，包括大大改善了左心室射血分数（EF）和分数缩短（FS）。此外，组织学和免疫组织化学成功地显示出LEF1 / hUCB-MSC减少的MI区和纤维化。我们发现LEF1 / hUCB-MSC的总体积极作用归因于干细胞在氧化应激条件下的增殖和存活增加以及LEF1分泌各种生长因子。结论，