Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Sci Rep. 2018 Jan 18;8(1):1160. doi: 10.1038/s41598-018-19417-8.
Identification of the adult cardiac stem cells (CSCs) has offered new therapeutic possibilities for treating ischemic myocardium. CSCs positive for the cell surface antigen c-Kit are known as the primary source for cardiac regeneration. Accumulating evidence shows that chemokines play important roles in stem cell homing. Here we investigated molecular targets to be utilized in modulating the mobility of endogenous CSCs. In a four week follow-up after experimental acute myocardial infarction (AMI) with ligation of the left anterior descending (LAD) coronary artery of Sprague-Dawley rats c-Kit+ CSCs redistributed in the heart. The number of c-Kit+ CSCs in the atrial c-Kit niche was diminished, whereas increased amount was observed in the left ventricle and apex. This was associated with increased expression of stromal cell-derived factor 1 alpha (SDF1α), and a significant positive correlation was found between c-Kit+ CSCs and SDF1α expression in the heart. Moreover, the migratory capacity of isolated c-Kit+ CSCs was induced by SDF1 treatment in vitro. We conclude that upregulation of SDF1α after AMI associates with increased expression of endogenous c-Kit+ CSCs in the injury area, and show induced migration of c-Kit+ cells by SDF1.
鉴定成人心肌干细胞（CSC）为治疗缺血性心肌提供了新的治疗可能性。已知细胞表面抗原 c-Kit 阳性的 CSCs 是心脏再生的主要来源。越来越多的证据表明趋化因子在干细胞归巢中发挥重要作用。在这里，我们研究了用于调节内源性 CSC 迁移性的分子靶标。在结扎 Sprague-Dawley 大鼠左前降支冠状动脉的实验性急性心肌梗死（AMI）后 4 周的随访中，c-Kit+CSC 在心脏中重新分布。心房 c-Kit 龛位中的 c-Kit+CSC 数量减少，而左心室和心尖部的数量增加。这与基质细胞衍生因子 1α（SDF1α）的表达增加有关，并且心脏中 c-Kit+CSC 和 SDF1α表达之间存在显著正相关。此外，体外 SDF1 处理诱导分离的 c-Kit+CSC 的迁移能力。我们得出结论，AMI 后 SDF1α 的上调与损伤区域内内源性 c-Kit+CSC 的表达增加有关，并显示 SDF1 诱导 c-Kit+细胞的迁移。
