Cardiovascular Research Laboratory, Center for Cardiovascular Research, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA.
Cardiovasc Res. 2010 Jul 1;87(1):40-9. doi: 10.1093/cvr/cvq027. Epub 2010 Jan 29.
Cell-based therapy for myocardial infarction (MI) holds great promise; however, the ideal cell type and delivery system have not been established. Obstacles in the field are the massive cell death after direct injection and the small percentage of surviving cells differentiating into cardiomyocytes. To overcome these challenges we designed a novel study to deliver cardiac progenitor cells as a cell sheet.
Cell sheets composed of rat or human cardiac progenitor cells (cardiospheres), and cardiac stromal cells were transplanted onto the infarcted myocardium after coronary artery ligation in rats. Three weeks later, transplanted cells survived, proliferated, and differentiated into cardiomyocytes (14.6 +/- 4.7%). Cell sheet transplantation suppressed cardiac wall thinning and increased capillary density (194 +/- 20 vs. 97 +/- 24 per mm(2), P < 0.05) compared with the untreated MI. Cell migration from the sheet was observed along the necrotic trails within the infarcted area. The migrated cells were located in the vicinity of stromal-derived factor (SDF-1) released from the injured myocardium, and about 20% of these cells expressed CXCR4, suggesting that the SDF-1/CXCR4 axis plays, at least, a role in cell migration. Transplantation of cell sheets resulted in a preservation of cardiac contractile function after MI, as was shown by a greater ejection fraction and lower left ventricular end diastolic pressure compared with untreated MI.
The scaffold-free cardiosphere-derived cell sheet approach seeks to efficiently deliver cells and increase cell survival. These transplanted cells effectively rescue myocardium function after infarction by promoting not only neovascularization but also inducing a significant level of cardiomyogenesis.
心肌梗死（MI）的细胞治疗具有很大的潜力；然而，理想的细胞类型和输送系统尚未建立。该领域的障碍是直接注射后大量的细胞死亡和存活细胞分化为心肌细胞的比例很小。为了克服这些挑战，我们设计了一项新的研究，以细胞片的形式输送心脏祖细胞。
在大鼠冠状动脉结扎后，将由大鼠或人心脏祖细胞（心脏球体）和心脏基质细胞组成的细胞片移植到梗死的心肌上。3 周后，移植的细胞存活、增殖，并分化为心肌细胞（14.6 +/- 4.7%）。与未经治疗的 MI 相比，细胞片移植抑制了心脏壁变薄并增加了毛细血管密度（194 +/- 20 对 97 +/- 24 个/平方毫米，P < 0.05）。从片上观察到细胞沿着梗死区内的坏死轨迹迁移。迁移的细胞位于从受损心肌释放的基质衍生因子（SDF-1）的附近，约 20%的这些细胞表达 CXCR4，表明 SDF-1/CXCR4 轴至少在细胞迁移中起作用。细胞片移植后，MI 后的心脏收缩功能得到保留，与未经治疗的 MI 相比，射血分数更高，左心室舒张末期压力更低。
无支架心脏球体衍生细胞片方法旨在有效地输送细胞并提高细胞存活率。这些移植的细胞通过促进血管生成和诱导显著水平的心肌发生，有效地挽救梗死后的心肌功能。
