Acute myocardial infarction (AMI) is a serious threat to human health. Stem cells can serve as ideal seed cells for myocardial repair and regeneration; however, insufficient homing to the infarcted areas and poor myocardial differentiation limit their further clinical application. Chemokine (C-X-C motif) ligand 12 (CXCL12) is an important stem cell homing factor, and Bone morphogenetic protein-2 (BMP2) is a differentiation-promoting factor. In this study, we designed microbubbleadenovirus complexes and investigated the functional benefit of co-delivery of Cxcl12 and Bmp2 genes in adenoviral vectors by ultrasound-targeted microbubble destruction (UTMD) for myocardial repair in AMI rats. By transfection of rat bone marrow mesenchymal stem cells (BMSCs), high transfection efficiency was achieved under ultrasound irradiation, and successful myocardial differentiation of the transfected BMSCs was induced after ultrasound-mediated-transfection of Bmp2in vitro. In the AMI rat model, co-delivery of Cxcl12 and Bmp2 at a ratio of 2:1 may result in significantly higher myocardial repair efficacy compared to transfection of Cxcl12 or Bmp2 only. Higher myocardial repairing efficacy was achieved with co-delivery of Cxcl12 and Bmp2 at a ratio of 2:1 than using a ratio of 1:1 or 1:2, as evidenced by smaller infarction size, higher micro-vessel density, and better recovery of cardiac function at 28 days after treatment. Hence, UTMD-mediated co-transfection of Cxcl12 and Bmp2 significantly promoted the repair/regeneration of the infarcted myocardium, thereby providing a promising approach for the repair of cardiac injury.

中文翻译：

---

超声靶向微泡破坏介导的Cxcl12（Sdf-1alpha）和Bmp2基因共同修复心肌。

急性心肌梗塞（AMI）对人类健康构成严重威胁。干细胞可以作为心肌修复和再生的理想种子细胞。然而，归巢不足的梗死区域和心肌分化差限制了它们的进一步临床应用。趋化因子（CXC基序）配体12（CXCL12）是重要的干细胞归巢因子，而骨形态发生蛋白2（BMP2）是分化促进因子。在这项研究中，我们设计了微气泡腺病毒复合物，并研究了共同递送Cxcl12和Bmp2的功能益处超声靶向微泡破坏（UTMD）在腺病毒载体中的基因对AMI大鼠的心肌修复。通过转染大鼠骨髓间充质干细胞（BMSCs），在超声照射下实现了高转染效率，并且在体外超声介导转染Bmp2后成功诱导了转染的BMSCs的心肌分化。在AMI大鼠模型中，与仅转染Cxcl12或Bmp2相比，以2：1的比例共同递送Cxcl12和Bmp2可能导致明显更高的心肌修复功效。通过共同递送Cxcl12和Bmp2获得更高的心肌修复功效治疗后28天，较小的梗死面积，较高的微血管密度和更好的心脏功能恢复证明，与2：1的比例相比，与1：1或1：2的比例更是如此。因此，UTMD介导的Cxcl12和Bmp2的共转染显着促进了梗塞心肌的修复/再生，从而为心脏损伤的修复提供了有希望的方法。