Su Gaofeng, Liu Liyun, Yang Lingjie, Mu Yuming, Guan Lina
Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Oncotarget. 2017 Dec 8;9(1):477-487. doi: 10.18632/oncotarget.23068. eCollection 2018 Jan 2.
Stem cells can promote myocardial regeneration and accelerate the formation of new blood vessels. As such, transplanted stem cells represent a promising treatment modality for acute myocardial infarction (AMI). Stem cells spontaneously home to the infarcted myocardium using chemotaxis, in which the stromal cell-derived factor (SDF-1α) has been shown to be one of the most important chemokines. However, spontaneously secreted SDF-1α is short-lived, and therefore does not meet the needs of tissue repair. In this study, adenoviruses carrying genes were loaded on microbubble carriers and the adenoviruses were released into AMI rats by ultrasound targeted microbubble destruction. The possibility of self-transplantation of bone marrow mesenchymal stem cells (BMSCs) induced by overexpression of SDF-1α in the infarcted myocardium was explored by detecting the number of BMSCs homing from the peripheral blood to the myocardial infarcts. The concentration of SDF-1α in peripheral blood was significantly higher after transfection, and the number of BMSCs was significantly higher in the peripheral blood and infarcted area. Further analyses indicated that the number of homing BMSCs increased with increased SDF-1α expression. In conclusion, our results suggest that ultrasound mediated transduction of exogenous SDF-1α genes into myocardial infarcted AMI rats can effectively promote the homing of endogenous BMSCs into the heart. Moreover, the number of homing stem cells was controlled by the level of SDF-1α expression.
干细胞可促进心肌再生并加速新血管形成。因此，移植干细胞是急性心肌梗死（AMI）一种很有前景的治疗方式。干细胞利用趋化作用自发归巢至梗死心肌，其中基质细胞衍生因子（SDF-1α）已被证明是最重要的趋化因子之一。然而，自发分泌的SDF-1α寿命短暂，因此无法满足组织修复的需求。在本研究中，携带基因的腺病毒被加载到微泡载体上，并通过超声靶向微泡破坏将腺病毒释放到AMI大鼠体内。通过检测从外周血归巢至心肌梗死部位的骨髓间充质干细胞（BMSC）数量，探索梗死心肌中SDF-1α过表达诱导BMSC自我移植的可能性。转染后外周血中SDF-1α浓度显著升高，外周血和梗死区域的BMSC数量显著增加。进一步分析表明，归巢BMSC的数量随SDF-1α表达增加而增加。总之，我们的结果表明，超声介导将外源性SDF-1α基因转导至心肌梗死的AMI大鼠体内可有效促进内源性BMSC归巢至心脏。此外，归巢干细胞的数量受SDF-1α表达水平控制。
